| 1. |
- Bjersing, Jan, 1966, et al.
(författare)
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Loss of ileal IgA+ plasma cells and of CD4+ lymphocytes in ileal Peyer's patches of vitamin A deficient rats.
- 2002
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Ingår i: Clinical and experimental immunology. - 0009-9104. ; 130:3, s. 404-8
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Tidskriftsartikel (refereegranskat)abstract
- Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm(2), P = 0.009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm(2), P = 0.009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm(2), P = 0.009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm(2), not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.
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| 2. |
- Dahlman-Höglund, Anna, 1964, et al.
(författare)
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Antibodies given orally in the neonatal period can affect the immune response for two generations: evidence for active maternal influence on the newborn's immune system.
- 1999
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Ingår i: Scandinavian journal of immunology. - 0300-9475. ; 50:6, s. 651-6
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Tidskriftsartikel (refereegranskat)abstract
- Two day old Wistar rats were tube fed with 1 or 10 micrograms of a mouse IgG1 monoclonal anti-idiotypic (a-Id) antibody that was directed against an anti-Escherichia coli-K13 capsular polysaccharide antibody. A control group was given 10 micrograms of an unrelated control antibody. Six weeks after the administration of antibodies, the rats were intestinally colonised with an ovalbumin (OVA)-producing E. coli O6K13 strain. At 8 weeks of age, the male rats (first generation) and the offsprings of the female rats (second generation), were parenterally immunised with OVA and dead wild type E. coli O6K13, and the immune response was followed. In the rats of the first generation, there were no major differences between the groups in the immune response to the bacterium. However, the offspring of the neonatally a-Id administered rats had a profoundly affected immune response to the idiotypically connected antigen K13, but also to other antigens on the bacteria. Thus, a-Id treatment in the first generation gave, in the second generation, a greatly enhanced serum antibody response to the spatially related antigens OVA and O6 LPS, as well as to the idiotypically connected antigen K13. Concurrently, the in vitro spleen cell proliferative response to both OVA and the wild type bacterium was lowered. Overall, greater effects were seen with the higher dose of a-Id. In conclusion, our results demonstrate that by giving monoclonal antibodies idiotypically connected to a single bacterial component to neonatal rats, one profoundly influence the immune response also to other-spatially related-bacterial antigens in their offsprings.
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| 3. |
- Dahlman-Höglund, Anna, 1964, et al.
(författare)
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Immune response against ovalbumin in rats colonized with an ovalbumin-producing Escherichia coli and the influence of feeding ovalbumin.
- 1994
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Ingår i: International archives of allergy and immunology. - 1018-2438. ; 105:4, s. 381-5
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Tidskriftsartikel (refereegranskat)abstract
- The influence of feeding ovalbumin (OA) on the development of IgE/IgG antibodies and delayed-type hypersensitivity (DTH) against OA was studied in rats colonized from birth with an Escherichia coli genetically manipulated to produce OA. At 21 days of age, colonized pups and pups with a normal intestinal flora were weaned onto either an OA-containing or a conventional diet without OA. At 2 months of age the colonized rats showed an increased DTH reaction to OA, but they did not have any anti-OA antibodies in serum. The rats were then immunized intracutaneously with OA in Freund's complete adjuvant. After immunization the colonized rats fed the conventional diet had a significantly higher DTH reaction to OA and significantly higher serum levels of IgE anti-OA antibodies than the uncolonized rats on the same diet. The colonized rats eating the OA-containing diet showed a 73% decrease in the DTH reaction to OA and also significantly lower levels of IgE and IgG antibodies against OA compared with the colonized rats fed conventional diet. The dams colonized as adults by the OA-producing E. coli developed IgE anti-lipopolysaccharide antibodies in serum while the pups colonized via the dams at birth did not. Neonatal colonization with an E. coli strain producing OA resulted in increased DTH reactivity against OA and priming for secondary IgE anti-OA response. Feeding the animals an OA-containing diet from weaning abrogated this intestinally induced hypersensitivity and rendered the animals orally tolerant to OA.
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| 4. |
- Dahlman-Höglund, Anna, 1964, et al.
(författare)
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Induction of IgE antibodies and T-cell reactivity to ovalbumin in rats colonized with Escherichia coli genetically manipulated to produce ovalbumin.
- 1992
-
Ingår i: Immunology. - 0019-2805. ; 76:2, s. 225-8
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Tidskriftsartikel (refereegranskat)abstract
- The immune response to ovalbumin (OA) and the bacterial antigens, lipopolysaccharide (LPS) and fimbriae were studied in conventional rats colonized from birth with an Escherichia coli strain producing OA. The colonized rats had developed IgE antibodies against OA, but not against the fimbrial or the LPS antigens from the E. coli at 2 months of age. At this time all rats were primed with OA given intracutaneously in Freund's complete adjuvant. Two weeks later the colonized rats showed a 35% greater delayed-type hypersensitivity (DTH) reaction to OA, measured as ear swelling, than the controls. Thus bacteria carrying antigens resembling potential allergens might aggravate, or participate in the induction of allergic symptoms. In addition such bacteria could be efficient vaccine vectors in protection against parasites. The study illustrates the importance of the mode of antigen presentation for the subsequent immune response.
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| 5. |
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| 6. |
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| 7. |
- Karlsson, Malin, et al.
(författare)
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"Tolerosomes” are produced by intestinal epithelial cells
- 2001
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Ingår i: European Journal of Immunology. ; 31, s. 2892-2900
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Tidskriftsartikel (refereegranskat)abstract
- The development of immunological tolerance to orally fed antigens depends on the sampling, processing and transportation events followed in the intestinal epithelium. We present here a description of a ’’tolerosome’’: a supra-molecular, exosome-like structure assembled in and released from the small intestinal epithelial cell. The tolerosome is a e 40 nm large vesicular structure that carries MHC class II (MHC II) with bound antigenic peptides sampled from the gut lumen. Tolerosomes isolated from serum shortly after antigen feeding or from an in vitro pulsed intestinal epithelial cell line are fully capable of inducing antigen specific tolerance in naive recipient animals. Purified tolerosomes represent a structure by which fed antigens can be efficiently presented to the immune system. Removal of the tolerosomes from serum by ultracentrifugation or absorption of MHC II results in abrogated tolerance development.
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| 8. |
- Lingman Framme, Jenny, 1977, et al.
(författare)
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Long-Term Follow-Up of Newborns with 22q11 Deletion Syndrome and Low TRECs
- 2022
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Ingår i: Journal of Clinical Immunology. - : Springer. - 0271-9142 .- 1573-2592. ; 42, s. 618-633
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based neonatal screening using T-cell receptor excision circles (TRECs) identifies infants with profound T lymphopenia, as seen in cases of severe combined immunodeficiency, and in a subgroup of infants with 22q11 deletion syndrome (22q11DS).Purpose: To investigate the long-term prognostic value of low levels of TRECs in newborns with 22q11DS.Methods: Subjects with 22q11DS and low TRECs at birth (22q11Low, N=10), matched subjects with 22q11DS and normal TRECs (22q11Normal, N=10), and matched healthy controls (HC, N=10) were identified. At follow-up (median age 16 years), clinical and immunological characterizations, covering lymphocyte subsets, immunoglobulins, TRECs, T-cell receptor repertoires, and relative telomere length (RTL) measurements were performed.Results: At follow-up, the 22q11Low group had lower numbers of naïve T-helper cells, naïve T-regulatory cells, naïve cytotoxic T cells, and persistently lower TRECs compared to healthy controls. Receptor repertoires showed skewed V-gene usage for naïve T-helper cells, whereas for naïve cytotoxic T cells, shorter RTL and a trend towards higher clonality were found. Multivariate discriminant analysis revealed a clear distinction between the three groups and a skewing towards Th17 differentiation of T-helper cells, particularly in the 22q11Low individuals. Perturbations of B-cell subsets were found in both the 22q11Low and 22q11Normal group compared to the HC group, with larger proportions of naïve B cells and lower levels of memory B cells, including switched memory B cells.Conclusions: This long-term follow-up study shows that 22q11Low individuals have persistent immunologic aberrations and increased risk for immune dysregulation, indicating the necessity of lifelong monitoring.Clinical Implications: This study elucidates the natural history of childhood immune function in newborns with 22q11DS and low TRECs, which may facilitate the development of programs for long-term monitoring and therapeutic choices.
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| 9. |
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| 10. |
- Admyre, C, et al.
(författare)
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Exosomes - nanovesicles with possible roles in allergic inflammation.
- 2008
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 63:4, s. 404-8
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Forskningsöversikt (refereegranskat)abstract
- Exosomes are nano-sized membrane vesicles which are released extracellularly after fusion of multivesicular endosomes with the cell membrane. Despite their characteristic composition of proteins compared to the cell membrane, no exosome-specific molecule has so far been characterized. Exosomes are found in bronchoalveolar lavage (BAL), urine, serum and breast milk, and are released from several cells implicated in allergy including mast cells, dendritic cells (DC), T cells and epithelial cells. Antigen-loaded exosomes have been shown to be highly immunogenic and we propose that exosomes could be a modulating factor in allergic responses. Allergen-presenting exosomes could transport allergen and stimulate allergen-specific T cells, and possibly also biasing T cell responses depending on the molecules present on the exosome surface. Furthermore, exosomes from mast cells, highly active in allergic reactions, have been found to induce DC maturation and also to be able to transport functional RNA to recipient cells, suggesting a new pathway for cell communication. Reversely, tolerizing exosomes e.g. tolerosomes, from gut or breast milk, could block an allergic response or prevent allergy development. A better understanding of the role of exosomes in allergies could make us understand how allergy can be prevented or lead to the development of more efficient treatments.
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| 11. |
- Albinsson, Sofie, et al.
(författare)
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Distinct populations of eosinophils in the human thymus with capacity to modulate thymocyte maturation.
- 2023
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 169:1, s. 57-68
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Tidskriftsartikel (refereegranskat)abstract
- Local differentiation of eosinophil precursors occurs in the human thymus. Thymic eosinophils are often positioned in the corticomedullary junction between the CD4+ CD8+ double-positive (DP) thymocytes and the CD4+ or CD8+ single-positive (SP) thymocytes. The aims of this study were to (1) determine if there are distinct thymic eosinophil populations that differ from the blood eosinophil populations and (2) evaluate the capacity of thymic eosinophils to promote the development of SP thymocytes from DP thymocytes. Thymic and blood eosinophils from thymectomized infants (n=7) were compared regarding the expression of 34 molecules using cytometry by time-of-flight (CyTOF). In addition, FACS-sorted thymic eosinophils were co-cultured with autologous CD3/CD28-stimulated DP, CD4 SP, and CD8 SP thymocytes and analysed by flow cytometry and CyTOF. X-shift clustering analysis and viSNE dimensionality reduction were performed. Seven eosinophil populations were identified within the blood and thymus, respectively, five of which were specific for either tissue. Whereas the blood eosinophil populations varied between individuals, the thymic eosinophil populations were more uniform. The eosinophil-thymocyte co-cultures resulted in (1) an increase in CD4 SP thymocytes when eosinophils were cultured with DP thymocytes, (2) decreased frequency of CD8 SP thymocytes when these were cultured with eosinophils, and (3) a more mature thymic phenotype when eosinophils were cultured with CD4 SP thymocytes. Thymic eosinophils are a specialized population of eosinophils with a distinct phenotype that separates them from their blood counterparts, and in vitro they appear to favour CD4 SP thymocyte development to the detriment of CD8 SP thymocytes.
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| 12. |
- Albinsson, Sofie, 1992, et al.
(författare)
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Eosinophils interact with thymocytes and proliferate in the human thymus
- 2021
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 51:6, s. 1539-1541
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils differentiate and mature in the thymus, outside of the bone marrow, in healthy individuals. Locally developed thymic eosinophils may contribute to the maturation and selection of human thymocytes.
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| 13. |
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| 14. |
- Ehn, Britt-Marie, 1962, et al.
(författare)
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Modification of IgE Binding to beta-Lactoglobulin by Fermentation and Proteolysis of Cow's Milk
- 2005
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Ingår i: J Agric Food Chem. ; 53:9
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Tidskriftsartikel (refereegranskat)abstract
- The effect of fermentation by Lactobacilli and of proteolytic hydrolysis of whole milk on the IgE binding ability of beta-lactoglobulin was studied using an ELISA inhibition assay. Sera from nine adult milk allergic patients were tested. The individual sera showed a similar inhibition pattern in the changes during fermentation and proteolysis. The degradation of beta-lactoglobulin was studied with liquid chromatography. In general, fermentation with Lactobacilli gave little effect on IgE binding, even though chromatography data showed a gradual degradation of beta-lactoglobulin. Proteolysis with trypsin, however, gave extensive degradation of beta-lactoglobulin and strongly decreased IgE binding. In addition, we measured the inhibition pattern of beta-lactoglobulin in various selected commercially available fermented milk products. These showed an IgE binding capacity similar to that of nonfermented high pasteurized milk.
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| 15. |
- Gale, Gita, et al.
(författare)
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Immunophenotype in orofacial granulomatosis with and without Crohn's disease.
- 2014
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Ingår i: Medicina oral, patología oral y cirugía bucal. - : Medicina Oral, S.L.. - 1698-6946. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this investigation was to characterise and compare the inflammatory infiltrates in patients with orofacial granulomatosis solely (OFG-S) and OFG with coexisting Crohn's disease (OFG+CD).
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| 16. |
- George-Chandy, Annie, 1969, et al.
(författare)
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Oral tolerance induction by mucosal administration of cholera toxin B-coupled antigen involves T-cell proliferation in vivo and is not affected by depletion of CD25+ T cells.
- 2006
-
Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 118:3, s. 311-20
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Tidskriftsartikel (refereegranskat)abstract
- Oral administration of antigens coupled to the B subunit of the cholera toxin (CTB) can dramatically reduce the amount of antigen needed for tolerance induction and has been used in several animal models to suppress conditions where the immune system overreacts to foreign and self-antigens. In this study, the cellular events following oral administration of CTB-coupled antigen was investigated. As a model system, limited numbers of CSFE-labelled cells from influenza haemagglutinin peptide (HApep) T-cell transgenic mice were transferred to wild type mice and the mice were then given CTB-coupled HApep orally. The inductive events of CTB-induced tolerance was characterized by extensive proliferation of HApep-specific T cells in the mesenteric lymph nodes (MLNs) and in the spleen. The proliferating cells up-regulated the gut homing molecule alpha4beta7 and down-regulated the high endothelial venule binding molecule L-selectin. Addition of the whole cholera toxin (CT) to CTB-HApep showed a similar pattern as CTB-HApep feeding, with antigen-specific proliferation in the MLN and spleen and expression of alpha4beta7 on the proliferating cells. However, addition of CT to CTB-HApep, produced a stronger and faster proliferative response and abrogated CTB-HA mediated oral tolerance. Feeding of CTB-HApep expanded CD25+ cells in the MLNs. CTB-induced oral tolerance could, however, not be explained by CD25+ dependent regulatory activity, as oral administration of CTB-HApep to mice depleted of CD25+ cells still gave rise to systemic tolerance. Thus, several mechanisms might co-orchestrate the systemic tolerance seen in response to feeding with CTB-coupled antigen.
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| 17. |
- Gunnar, Ronquist, et al.
(författare)
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Exosomen-intercellulär signalbärare med framtidspotential
- 2013
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Ingår i: Läkartidningen. - 0023-7205. ; 110:46
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Tidskriftsartikel (refereegranskat)abstract
- Exosomer frisätts från kroppens alla celler. De utgör ett nyupptäckt intercellulärt signalsystem. Välstuderade områden är immunologi, inflammation och allergi med applikation inom bla cancervård, urologi och kardiologi. Man kan förvänta sig att exosomer kommer att kunna användas inom både diagnostik och terapi.
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| 18. |
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| 19. |
- Herías, M V, et al.
(författare)
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Immunomodulatory effects of Lactobacillus plantarum colonizing the intestine of gnotobiotic rats.
- 1999
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 116:2, s. 283-90
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Tidskriftsartikel (refereegranskat)abstract
- We have studied the effect of the probiotic strain Lactobacillus plantarum 299v on the immune functions of gnotobiotic rats. One group of germ-free rats was colonized with the type 1-fimbriated Escherichia coli O6:K13:H1 and another group with the same E. coli strain together with L. plantarum 299v. One and 5 weeks after colonization, bacterial numbers were determined in the contents of the small intestine, caecum and mesenteric lymph nodes. Small intestinal sections were examined for CD8+, CD4+, CD25+ (IL-2R alpha-chain), IgA+ and MHC class II+ cells and mitogen-induced spleen cell proliferation was determined. Immunoglobulin levels and E. coli-specific antibodies were measured in serum. Rats given L. plantarum in addition to E. coli showed lower counts of E. coli in the small intestine and caecum 1 week after colonization compared with the group colonized with E. coli alone, but similar levels after 5 weeks. Rats colonized with L. plantarum + E. coli had significantly higher total serum IgA levels and marginally higher IgM and IgA antibody levels against E. coli than those colonized with E. coli alone. They also showed a significantly increased density of CD25+ cells in the lamina propria and displayed a decreased proliferative spleen cell response after stimulation with concanavalin A or E. coli 1 week after colonization. The results indicate that L. plantarum colonization competes with E. coli for intestinal colonization and can influence intestinal and systemic immunity.
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| 20. |
- Hultkrantz, Susanne, 1977, et al.
(författare)
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Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration.
- 2005
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Ingår i: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 116:3, s. 362-72
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11.10 mice were less dependent on transforming growth factor (TGF)-beta for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens.
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| 21. |
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| 22. |
- Karlsson, Anna, 1967, et al.
(författare)
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Galectin-3 functions as an opsonin and enhances the macrophage clearance of apoptotic neutrophils.
- 2009
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Ingår i: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 19:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- Galectin-3, a beta-galactoside binding, endogenous lectin, takes part in various inflammatory events and is produced in substantial amounts at inflammatory foci. We investigated whether extracellular galectin-3 could participate in the phagocytic clearance of apoptotic neutrophils by macrophages, a process of crucial importance for termination of acute inflammation. Using human leukocytes, we show that exogenously added galectin-3 increased the uptake of apoptotic neutrophils by monocyte-derived macrophages (MDM). Both the proportion of MDM that engulfed apoptotic prey and the number of apoptotic neutrophils that each MDM engulfed were enhanced in the presence of galectin-3. The effect was lactose-inhibitable and required galectin-3 affinity for N-acetyllactosamine, a saccharide typically found on cell surface glycoproteins, since a mutant lacking this activity was without effect. The enhanced uptake relied on the presence of galectin-3 during the cellular interaction and was paralleled by lectin binding to apoptotic cells as well as MDM in a lactose-dependent manner. These findings suggest that galectin-3 functions as a bridging molecule between phagocyte and apoptotic prey, acting as an opsonin. The process of clearance, whereby apoptotic neutrophils are removed by macrophages, is crucial for the resolution of acute inflammation and our data imply that the increased levels of galectin-3 often found at inflammatory sites could potently affect this process.
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| 23. |
- Korotkova, Marina, 1954, et al.
(författare)
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Modulation of neonatal immunological tolerance to ovalbumin by maternal essential fatty acid intake
- 2004
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Ingår i: Pediatr Allergy Immunol. - 0905-6157. ; 15:2, s. 112-22
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Tidskriftsartikel (refereegranskat)abstract
- The present study examines whether dietary essential fatty acid (EFA) intake influences the induction of oral tolerance to ovalbumin (OA) in neonatal and adult rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet supplemented (S) with EFA (7% soybean oil), or a diet deficient (D) in EFA (7% hydrogenated lard). The rat offspring were subsequently exposed to OA either via the milk at 10-16 days (neonatal rats), or as adults via the drinking water at 7-9 wk of age. Oral administration of OA to the adult rats lead to suppression of the delayed-type hypersensitivity (DTH) reactivity and IgG antibody response against OA, which was not influenced by their diets. In the offspring of the dams fed the D diet antigen exposure via the milk resulted in suppression of the serum antibody levels and DTH reaction against OA indicating induction of oral tolerance. Higher transforming growth factor beta (TGF-beta) mRNA levels in the draining lymph nodes suggested this to be mediated by regulatory T cells. In contrast, OA exposure of the dams fed the S diet did not result in a suppressed OA response of their offspring. Thus, the quality of FA ingested by the mother may have effects on the development of immunological tolerance to dietary antigens in the offspring. Our results might have importance for the understanding of the increase in allergy related to the Western type of diet.
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| 24. |
- Korotkova, Marina, 1954, et al.
(författare)
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The ratio of n-6 to n-3 fatty acids in maternal diet influences the induction of neonatal immunological tolerance to ovalbumin
- 2004
-
Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:2, s. 237-44
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Tidskriftsartikel (refereegranskat)abstract
- Prevalence of allergy is increasing in many countries and might be related to changed environmental factors, such as dietary fatty acids (FA). The present study investigates whether dietary ratio of n-6 to n-3 FA influences the induction of immunological tolerance to ovalbumin (OA) in neonatal rats. During late gestation and throughout lactation Sprague-Dawley rats were fed a diet containing 7% linseed oil (n-3 diet), sunflower oil (n-6 diet) or soybean oil (n-6/n-3 diet). At 10-16 days of age the rat offspring were subsequently exposed, or not, to OA via the milk. The offspring were weaned onto the same diets as the mothers and immunized with OA and the bystander antigen human serum albumin (HSA). In the offspring on the n-3 diet exposure to OA via the milk resulted in lower delayed type hypersensitivity reaction (DTH) and antibody responses against both OA and HSA, compared to those in the offspring not exposed to OA, indicating the induction of oral tolerance. In the offspring on the n-6 diet, the exposure to OA led to depressed specific immune responses against only OA, not HSA. In the offspring on the n-6/n-3 diet oral exposure to OA did not influence immune responses against OA, or HSA. The results indicate that the dietary ratio of n-6/n-3 FA is important for the induction of neonatal oral tolerance. Thus nonoptimal feeding may have effects on the development of immunological tolerance to dietary antigen ingested by the mother. The ratio of n-6/n-3 FA in the diet may be considered in the context of increased prevalence of allergy.
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| 25. |
- Lasaitiene, Daina, 1970, et al.
(författare)
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Perturbed medullary tubulogenesis in neonatal rat exposed to renin-angiotensin system inhibition.
- 2003
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - 0931-0509. ; 18:12, s. 2534-41
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacological interruption of the angiotensin II type-1 receptor (AT(1)) signalling during nephrogenesis in rats induces irreversible abnormalities in kidney morphology, comprising papillary atrophy and tubulointerstitial damage, which are characterized by tubular dilatation/atrophy and interstitial inflammation/fibrosis. This study determined the time course for development of tubular structural and inflammatory changes and possible cytokine production in the renal medulla of newborn rats exposed to angiotensin-converting enzyme (ACE) inhibition. Additionally, medullary expression of E-cadherin, a marker for tubular formation, was investigated in ACE-inhibited rats.
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| 26. |
- Lin, Xiao Ping, et al.
(författare)
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Human small intestinal epithelial cells constitutively express the key elements for antigen processing and the production of exosomes.
- 2005
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Ingår i: Blood cells, molecules & diseases. - : Elsevier BV. - 1079-9796. ; 35:2, s. 122-8
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Tidskriftsartikel (refereegranskat)abstract
- In humans, the small intestinal epithelial cells (IEC) have a high constitutive expression of MHC class II (MHC II), and contains lysosomes. The IEC also contains MHC II rich multivesicular compartments and has been shown to produce exosomes. This suggests a role for the IEC in antigen processing and presentation either directly or indirectly by the production of exosomes. However, the presence and localisation in the IEC of other key molecules involved in this process has not been studied previously. In the present work, we have investigated small intestinal biopsies from healthy adults and the HT29 IEC cell line with monoclonal antibodies against molecules involved in the antigen processing/presenting systems and molecules typically found on exosomes derived from professional APCs and IECs. Immunohistology was performed to study the expression and localisation of MHC II (HLA-DR), HLA-DM, MHC I (HLA-ABC), CD1d, Invariant chain, Lamp-1, CD68, CD63, B7.1, B7.2, ICAM-1, Cathepsin D/S/L and the IEC specific marker A33 in the IECs. We found that the IECs from the biopsies constitutively express MHC II, HLA-DM, MHC I, Invariant chain, Lamp-1, CD 68, CD63 and A33, and these markers were also found in the IFN-g treated HT-29 cells. All these molecules were found apically in the IECs of the biopsies, localised mainly in vesicular structures. Interestingly, in the baso-latereral area of the IEC, only MHC II, MHC I, Lamp 1, CD68, CD63 and A33 were found and also here with vesicular staining pattern which matches the molecules previously found on exosomes derived professional APCs and human IEC lines. CD1d, B7, ICAM-1, CD9 and cathepsin D and L were absent in the IEC compartment, but cathepsin S showed a relatively weak staining in the apical part of the IEC. The staining pattern and the morphological localisation of these markers suggest a prominent antigen processing/loading and trafficking compartment, and a possible baso-lateral release of exosomes in the normal human IEC.
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| 27. |
- Lin, Xiao Ping, et al.
(författare)
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Local allergic reaction in food-hypersensitive adults despite a lack of systemic food-specific IgE
- 2002
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Ingår i: J Allergy Clin Immunol. ; 109:5 Pt 1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Objective tools are lacking for the diagnosis of local gastrointestinal inflammatory reactions in skin prick test (SPT)-negative and serum IgE antibody (s-IgE Ab)-negative patients with suspected food allergy. OBJECTIVE: The purpose of this investigation was to evaluate the presence of eosinophils, T cells, local IgE-bearing cells, IL-4, and IFN-gamma in small intestinal biopsy specimens from adult SPT-negative/s-IgE Ab-negative patients with food allergy during symptomatic and nonsymptomatic periods. METHODS: Fourteen patients with food allergy-related gastrointestinal symptoms confirmed by double-blinded, placebo-controlled food challenge (DBPCFC) were investigated. Eleven of the patients were SPT-negative and s-IgE Ab-negative. Sex- and age-matched healthy volunteers were used as controls. Duodenal biopsies were studied with immunostaining through use of a panel of mouse monoclonal antibodies specific for eosinophils, CD3, CD4, CD8, IgE, IL-4, and IFN-gamma. RESULTS: Significant increases in numbers of MBP(+) eosinophils, IgE-bearing cells, and T cells were found in the duodenal mucosa of the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with healthy controls. Numbers of IL-4(+) cells were increased and numbers of IFN-gamma(+) cells were reduced in the patients when they were symptomatic in comparison with when they were asymptomatic and in comparison with the controls. There were no differences in total s-IgE levels between any of the groups. CONCLUSION: A significant correlation was found between the appearance of symptoms of food hypersensitivity and the duodenal presence of IgE-bearing cells, activated eosinophils, and T cells in patients with negative SPT results and negative s-IgE Ab to the offending food. We suggest that a localized IgE-mediated response caused the gastrointestinal symptoms seen in these patients.
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| 28. |
- Lundberg, Vanja, et al.
(författare)
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Thymic exosomes promote the final maturation of thymocytes
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Extensive knowledge has been gained the last years concerning mechanisms underlying the selection of single positive thymocytes in the thymic medulla. Less is known regarding other important processes in the thymic medulla such as the regulation of late stage thymocyte maturation. We have previously reported that exosomes are abundant in the thymus with a phenotype that indicates an epithelial cell origin and immunoregulatory properties. In this study we use an in vitro system to investigate the effects of thymic exosomes on the maturation of single positive thymocytes as well as effects on nTreg formation. We show that thymic exosomes promote the maturation of single positive CD4(+)CD25(-) cells into mature thymocytes with S1P(1)(+)Qa2(+) and CCR7(+)Qa2(+) phenotypes. Furthermore, we show that thymic exosomes reduce the formation of CD4(+)CD25(+)FoxP3(+) thymocytes and that these exosome effects are independent of dendritic cell co-stimulation but require intact exosomal RNA content and surface proteins. An efficient direct uptake of exosomes by both thymocytes and thymic DC's is also demonstrated. In conclusion, this study demonstrates that exosomes may represent a new route of communication within the thymus.
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| 29. |
- Lundell, Anna-Carin, 1976, et al.
(författare)
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IFN type I and II induce BAFF secretion from human decidual stromal cells
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers' children exhibit higher BAFF levels in cord blood than non-farmers' children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-gamma and IFN-alpha, and NK cells and NK-T-like cells competent of IFN-gamma production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.
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| 30. |
- Lundqvist, Christina, 1988, et al.
(författare)
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Switched CD21-/low B cells with an antigen-presenting phenotype in the infant thymus.
- 2019
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Ingår i: The Journal of allergy and clinical immunology. - : Elsevier BV. - 1097-6825 .- 0091-6749. ; 143:4
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Tidskriftsartikel (refereegranskat)abstract
- Half of all B cells in the human thymus are mature CD21-/low AIRE-expressing cells with a professional antigen presenting cell phenotype, implying a role in T-cell selection and therefore critical in preventing autoimmunity.
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| 31. |
- Lönnqvist, Anna, 1980, et al.
(författare)
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Neonatal exposure to staphylococcal superantigen improves induction of oral tolerance in a mouse model of airway allergy.
- 2009
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Ingår i: European journal of immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 39:2, s. 447-56
-
Tidskriftsartikel (refereegranskat)abstract
- The hygiene hypothesis suggests that lack of microbial stimulation in early infancy may lead to allergy, but it has been difficult to identify particular protective microbial exposures. We have observed that infants colonised in the first week(s) of life with Staphylococcus aureus have lower risk of developing food allergy. As many S. aureus strains produce superantigens with T-cell stimulating properties, we here investigate whether neonatal mucosal exposure to superantigen could influence the capacity to develop oral tolerance and reduce sensitisation and allergy. BALB/c mice were exposed to staphylococcal enterotoxin A (SEA) as neonates and fed with OVA as adults, prior to sensitisation and i.n. OVA challenge. Our results show that SEA pre-treated mice are more efficiently tolerised by OVA feeding, as shown by lower lung-cell infiltration and antigen-specific IgE response in the SEA pre-treated mice, compared with sham-treated mice. This was not due to deletion or anergy of lymphocytes by SEA treatment, because the SEA pre-treated mice that were fed with PBS showed similar inflammatory response as the sham-treated PBS-fed mice. Our results suggest that strong T-cell activation in infancy conditions the mucosal immune system and promotes development of oral tolerance.
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| 32. |
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| 33. |
- Magnusson, J, et al.
(författare)
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A kinetic study in adults with food hypersensitivity assessed as eosinophil activation in fecal samples
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 33:8, s. 1052-1059.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immune-mediated food hypersensitivity affecting the gut is difficult to evaluate, and objective tools to diagnose local gastrointestinal (GI) inflammatory reactions are lacking. OBJECTIVES: To determine whether allergic manifestations in adults with a history of food-related GI symptoms could be assessed in feces during symptomatic and non-symptomatic periods, using the surrogate markers, eosinophil cationic protein (ECP), eosinophil protein X (EPX) and myeloperoxidase (MPO). METHODS: Thirteen subjects with food hypersensitivity-related GI symptoms, confirmed by a positive double-blind placebo-controlled food challenge (DBPCFC), were subjected to an open kinetic food challenge design for 6 weeks. Symptoms were recorded and scored during the 3-week study period and stool samples were obtained every day. The surrogate markers ECP, EPX and MPO were measured in the supernatants from feces samples. RESULTS: A significant increase in abdominal pain, distension and flatulence was observed during challenge, with a gradual decrease during elimination diet. Both between days and subjects, EPX levels were more frequently increased compared to ECP and MPO. Individuals with a history of a short duration of symptoms had significantly higher mean levels of EPX and MPO than those with a longer duration of symptoms. CONCLUSIONS: An overall increase in levels of eosinophil markers, in particular EPX, was observed in feces from patients with food-related GI symptoms. However, rather than being a tool to differentiate symptomatic from non-symptomatic periods, EPX might be used for detecting an ongoing clinical or subclinical chronic inflammation, that may have an impact on the patient's clinical course of GI symptoms.
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| 34. |
- Magnusson, Jenny, 1970, et al.
(författare)
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Seasonal intestinal inflammation in patients with birch pollen allergy
- 2003
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Ingår i: J Allergy Clin Immunol. ; 112:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The pathophysiologic interactions of inflammatory reactions between the mucosa of the respiratory tract and that of the gastrointestinal tract in individuals with allergy are poorly studied, despite the fact that allergic symptoms in the airways and the gastrointestinal tract might arise in the same patient. OBJECTIVE: The objective of this study was to examine the inflammatory response histologically by enumerating eosinophils, IgE+ cells, and T cells in duodenal biopsy specimens in adult patients with IgE-mediated birch pollen allergy during the birch pollen season and off-season. METHODS: Nine patients with birch pollen allergy verified by skin prick test and serum IgE antibodies were investigated toward the end of the birch pollen season and again 6 months later (off-season). Duodenal biopsy specimens were obtained and studied by immunostaining for the eosinophil major basic protein (MBP), IgE, and CD3+ T cells. RESULTS: Oral allergy syndrome to birch-associated foods was present in all patients as indicated by questionnaire. Duodenal increases of MBP+ eosinophils and IgE-bearing cells were found in the patients during the birch pollen season as compared with off-season. No seasonal differences in the T-cell numbers in these patients were seen. Off-season, there was no significant difference between the patients and the control subjects regarding the intestinal frequencies of MBP+ eosinophils, mucosal IgE+ cells, and T cells. CONCLUSION: Birch pollen exposure triggered a local inflammation with an increase in duodenal eosinophils and IgE-carrying mast cells in patients with allergy. Our study gives evidence for the interplay between immunologically active cells in the airways and the gut.
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| 35. |
- Morris, Olivia Claire, et al.
(författare)
-
Constitutively low expression of collagen XIII alpha 1 may help explain the vulnerability of the inferior rectus muscle to thyroid-associated ophthalmopathy
- 2016
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Ingår i: Orbit. - : Informa UK Limited. - 0167-6830 .- 1744-5108. ; 35, s. 343-349
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Taylor & Francis. Thyroid-associated ophthalmopathy (TAO) has a predilection for inferior rectus muscle that has never been explained. We conducted immunohistochemical staining for the soluble cleaved form of collagen XIII alpha 1 (COL13A1) and found constitutively low expression of COL13A1 in normal human inferior rectus muscles and moderate expression of COL13A1 in normal human medial rectus muscles. COL13A1 is known to be essential to development and maintenance of neuromuscular junctions and there is some evidence to suggest it may help support normal immune function. The combination of constitutively low expression of COL13A1, high physiological and metabolic demands, and consequentially relatively high exposure to stressors via the blood stream may help explain the particular vulnerability of inferior rectus to TAO compared to other extraocular muscles.
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| 36. |
- Morris, Olivia Claire, et al.
(författare)
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Overexpression of collagen XIII in extraocular fat affected by active thyroid-associated ophthalmopathy: A crucial piece of the puzzle?
- 2016
-
Ingår i: Orbit. - : Informa UK Limited. - 0167-6830 .- 1744-5108. ; 35:4, s. 227-232
-
Tidskriftsartikel (refereegranskat)abstract
- Thyroid-associated ophthalmopathy (TAO) causes irreversible increase in extraocular fat volume that contributes to the risk of exophthalmos and compressive optic neuropathy. Collagen XIII is implicated in uncontrolled cell growth in some tumours, but we are not aware of any studies of collagen XIII in TAO-affected solid tissue to date. We conducted immunohistochemical staining for collagen XIII alpha 1 (COL13A1), present in both the transmembrane and cleaved forms of collagen XIII, in consecutive prospectively collected human extraocular tissue specimens from patients with TAO and controls. We identified overexpression of collagen XIII in active TAO-affected fat. We discuss how species and cell-type specific responses of collagen XIII to stressors may help explain the different phenotypes of TAO. © 2016 Taylor & Francis.
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| 37. |
- Nurkkala, Merja, 1966, et al.
(författare)
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MHC expression and chemokine production in the murine vagina following intra-vaginal administration of ligands to toll-like receptors 3, 7 and 9
- 2007
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Ingår i: J Reprod Immunol. - : Elsevier BV. - 0165-0378. ; 73:2, s. 148-57
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Tidskriftsartikel (refereegranskat)abstract
- The expression of MHC class I, MHC class II and the chemokines IP-10, MIP-1alpha, RANTES, fractalkine and I-TAC has been analyzed after intra-vaginal treatment with three synthetic toll-like receptors (TLR) agonists-double-stranded RNA (poly I:C), imiquimod and CpG-rich oligonucleotides (CpG-ODN). These compounds act mainly through TLR3, TLR7 and TLR9, respectively. CpG-ODN induced an accumulation of leucocytes in the vagina, and a strong up-regulation of MHC class I expression on both leucocytes and epithelial cells. Imiquimod and poly I:C induced a weak MHC class I up-regulation in the epithelium but not in the lamina propria. Neither treatment had any profound effect on expression of MHC class II on epithelial cells but poly I:C and to a lesser extent CpG-ODN, up-regulated MHC class II staining intensity which, in the case of CpG-ODN, treatment, was associated with a strong accumulation of CD11c-positive dendritic cells. All three treatments induced an early (8h) but transient IP-10 response. Imiquimod and CpG-ODN, but not poly I:C induced an early MIP-1alpha response which remained for at least 7 days in CpG-ODN-treated animals but not in imiquimod-treated mice. Poly I:C and CpG-ODN, but not imiquimod, induced significant levels of RANTES at different time-points post-treatment. None of the treatments induced any significant changes in the levels of fractalkine, I-TAC or IFN-alpha. These studies have implications for the manipulation of the genital immune response and also improving the outcome of vaginal immunotherapy.
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| 38. |
- Rask, Carola, 1970, et al.
(författare)
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A full flora, but not monocolonization by Escherichia coli or lactobacilli, supports tolerogenic processing of a fed antigen.
- 2005
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:6, s. 529-35
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Tidskriftsartikel (refereegranskat)abstract
- Fed protein undergoes processing and coupling to major histocompatibility complex (MHC) II molecules during passage through the intestinal epithelium, generating a tolerogenic form of the antigen in serum. Transfer of this factor to naïve animals induces tolerance in the recipient. In this study, we investigate what impact colonization with Gram-positive (Lactobacillus plantarum) or Gram-negative (Escherichia coli) bacteria has on tolerogenic processing in the gut. Germ-free (GF), monocolonized or conventional mice were fed ovalbumin (OVA), and their serum was collected and transferred to naïve conventional recipients that were tested for delayed-type hypersensitivity against OVA after parenteral immunization. A transferable tolerogenic factor was produced by conventional mice, but not by mice that were germ free or monocolonized with either E. coli or L. plantarum. Conventional, but neither GF nor monocolonized mice showed upregulation of MHCII expression in the epithelium of small intestine. The results suggest that a complex intestinal microflora is needed to support oral tolerance development.
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| 39. |
- Ravi Sharma, Dulal, 1987, et al.
(författare)
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Human Milk: Its Components and Their Immunobiologic Functions
- 2015
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Ingår i: Mucosal Immunology: Fourth Edition. Volume 2. - : Elsevier. - 9780124158474 ; , s. 2307-2341
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Whereas a neonate is born is sterile, immediate exposure to its mother's mucosal surfaces allows it to acquire microflora, which plays an important role in defense against potential pathogens. This initial stimulus helps the immature immune system of the newborn to develop the capacity to respond with specific immunologic tolerance while avoiding the development of allergic and autoimmune disease. Breast-feeding provides nutritional and developmental, along with anti-infectious, advantages to the infant. The significant protection conferred by breast-feeding against varied infections such as acute and prolonged diarrhea, neonatal septicemia, respiratory tract infections, acute and recurrent otitis media, and urinary tract infections is observed worldwide. Human breast milk contains numerous components, including antibodies, cytokines, hormones, enzymes, and major proteins with multiple activities (microbicidal, tumoricidal, anti-inflammatory, autoimmune, etc.). Breast-feeding can strikingly reduce infant mortality, as well as the fertility of the breast-feeding mother. In this manner, breast-feeding provides significant benefits for lactating mothers and their offspring, in addition to society as a whole. © 2015 Elsevier Inc. All rights reserved.
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| 40. |
- Rentzos, Georgios K., et al.
(författare)
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Intestinal allergic inflammation in birch pollen allergic patients in relation to pollen season, IgE sensitization profile and gastrointestinal symptoms
- 2014
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 4:19
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Birch pollen allergic patients frequently experience gastrointestinal upset accompanied by a local allergic inflammation in the small intestine especially during the pollen season. However, it is not known if the GI pathology is connected to the subjective symptoms of the patient. The objective of this study was to evaluate the immune pathology of the duodenal mucosa and the serum IgE antibody profiles in birch pollen allergic patients in relation to their gastrointestinal symptoms, during and outside the birch pollen season. Methods: Thirty-two patients with birch pollen allergy and sixteen healthy controls were enrolled in the study. Twenty allergic patients had gastrointestinal symptoms and twelve did not. All participants underwent an allergy investigation and gastroscopy with duodenal biopsy. The duodenal biopsies were retrieved during the pollen season (May-June) and off-season (November-March). The biopsies were immunostained for mast cells (IgE and tryptase), eosinophils, T cells (CD3), and dendritic cells (CD11c). Pollen-specific IgE antibodies were determined by ImmunoCAP and component microarray (ISAC). Results: Patients in both pollen allergic groups showed similar degree of intestinal allergic inflammation during the pollen season regardless of gastrointestinal symptoms. The eosinophils, mast cells and dendritic cells were increased in the mucosa. Patients with gastrointestinal symptoms had significantly elevated IgE antibodies to birch (rBet v 1), hazelnut (rCor a 1), and apple (rMal d1) during the pollen season. Conclusions: Patients allergic to birch pollen have clear signs of an ongoing allergic inflammation in their intestinal mucosa, which is aggravated during the pollen season. The magnitude of the allergic intestinal inflammation is not associated with subjective gastrointestinal symptoms of the individual patient. © 2014 Rentzos et al.; licensee BioMed Central Ltd.
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| 41. |
- Rentzos, Georgios K., et al.
(författare)
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Prevalence of food hypersensitivity in relation to IgE sensitisation to common food allergens among the general adult population in West Sweden
- 2019
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe prevalence of self-experienced adverse reactions to foods seems to have an increasing trend in both adults and children. However, it is unclear if the prevalence of food hypersensitivity in the Swedish adult population is still rising, what symptoms are caused by different foods and which are the most common foods to which adults are more frequently IgE-sensitised.MethodsIn a cross-sectional study based on questionnaire responses, interviews and clinical examinations as part of the West Sweden Asthma Study, 1042 subjects from the general population, 17-78years of age, living in Vastra Gotaland, Sweden, were included. The subjects reported symptoms for 56 specified foods and blood samples were taken to examine the IgE-sensitisation pattern for 9 common foods.ResultsApproximately 32% of adults reported food hypersensitivity, affecting mostly women and subjects less than 61years old. The foods most often reported to cause adverse reactions were hazelnut (8.9%), apple (8.4%), milk (7.4%) and kiwi (7.3%). Less than one percent (0.9%) reported symptoms from ingestion of meat. Symptoms mostly affected the gastrointestinal tract (15%) and the skin (2.7%). Sixteen per cent were IgE-sensitised to common foods, most often to hazelnut (13.3%), peanut (4.9%) and almond (3.0%), while 5.9% reported symptoms and were IgE-sensitised to the same food, mainly to hazelnut (5.3%).ConclusionsThe prevalence of self-reported food hypersensitivity in West Sweden indicates a rising trend. The correspondence between self-reported symptoms and IgE-sensitisation to foods is generally poor, except for hazelnut and almond which exhibit moderate or fair correlation.
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| 42. |
- Rentzos, Georgios K., et al.
(författare)
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Self-reported adverse reactions and IgE sensitization to common foods in adults with asthma
- 2015
-
Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 5:25
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is very few data available on the prevalence of food hypersensitivity among adults with asthma. The aim of this study was to explore the prevalence of self-reported adverse reactions and IgE sensitization to the different foods and to determine the spectrum and the prevalence of food-related gastrointestinal symptoms in adults with and with no asthma. Methods: A cross sectional study based on interviews and questionnaire responses from 1527 subjects, aged 18-75 years of age, from Västra Götaland in Sweden, as part of the larger West Sweden Asthma Study. IgE analyses were performed in sera from all subjects. Results: Fifty three percent of adults with asthma reported adverse reactions to foods compared to 30 % of non-asthmatics. Most asthmatics reported symptoms from eating hazelnut, followed by other nuts, birch-related foods, milk, peanut and shellfish. Furthermore, adults with asthma experienced significantly more often gastrointestinal symptoms from hazelnut, apple and milk and were found to significantly more often be sensitized to the most common foods compared to the non-asthmatic subjects. The asthmatics showed a significant correlation between IgE to both hazelnut and birch and self-reported symptoms after ingestion of hazelnut and to a lesser extent to almonds. Conclusions: The prevalence of self-reported adverse reactions and sensitization to the most common foods was much higher among the asthmatic subjects. Hazelnut was the food that asthmatics most frequently experienced adverse reactions from, and the strong correlation between IgE to hazelnut and birch indicate that the observed adverse reactions are partly due to sensitization to allergens from the PR-10 family. © 2015 Rentzos et al.
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| 43. |
- Rentzos, Georgios K., et al.
(författare)
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Use of a basophil activation test as a complementary diagnostic tool in the diagnosis of severe peanut allergy in adults
- 2015
-
Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Diagnosis of severe peanut allergy is difficult and delays in making an accurate diagnosis may place the patient at risk. Adults with a history of anaphylaxis must strictly avoid any contact with peanuts or products that may contain traces of peanuts. For these persons, conventional evaluations with skin prick testing (SPT) and IgE tests may not be sufficient to assess the risk of anaphylaxis. Therefore, we investigated whether the basophil activation test (BAT) could be used for the diagnosis of severe peanut allergy in adults. We compared the non-invasive BAT with conventional laboratory diagnostic tests, including SPT and specific IgE to allergen extracts and components, for the diagnosis of severe peanut allergy. Methods: Forty-seven persons with severe allergy to peanuts and a clinical diagnosis of anaphylaxis (PA-group), 22 subjects with peanut sensitization (PS-group) and 22 control (C-group) subjects, all in the age range of 18-60 years, were recruited retrospectively and prospectively into the study. Thirty-four patients with peanut allergy and 11 peanut-sensitized patients were sensitized to soy, while 36 patients in the PA-group and 20 patients in the PS-group were sensitized to birch pollen. All the patients and control subjects were investigated with BAT and SPT for responses to peanut, soy and birch extracts and their serum samples were assayed for the presence of specific IgE to peanut, soy and birch extracts, as well as IgE to allergen components (ISAC). Results: In a multivariate factor analysis, severe peanut allergy (PA) was positively associated with SPT to peanut, IgE to peanut, BAT to peanut and IgE to rAra h 1, 2, 3 and 6 peanut components, as well as to soy components (nGly m 5 and nGly m 6). In contrast, peanut sensitization was positively associated with increased levels of IgE to rAra h 8, birch and birch-related components. BAT-detected reactivity to peanut was significantly higher in patients who had a history of severe allergy to peanuts, as compared with patients who were sensitized to peanuts (p < 0.001), and the receiver operating curve (ROC) analysis showed that BAT had high sensitivity and specificity for predicting severe peanut allergy, with a ROC area under the curve of 0.862. However, in the PA-group, the BAT results for peanut correlated only weakly with the levels of IgE to rAra h 1, 2 and 3 and nAra h 6. Study limitations: oral provocation in the patients with a history of severe peanut allergy could not be performed to compare clinical reactivity with the BAT result due to ethical constraints. Neither was it possible to perform BAT with peanut recombinant allergens which were not available at the time the study commenced Conclusions: BAT is useful in determining the severity of peanut allergy and may be used as a complementary diagnostic tool to ensure accurate diagnosis of severe peanut allergy in adults. Thus, it may reduce the need to subject these patients to further tests, including an open challenge with peanuts. © 2015 Rentzos et al.; licensee BioMed Central.
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| 44. |
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| 45. |
- Skogberg, Gabriel, et al.
(författare)
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Altered expression of autoimmune regulator in infant down syndrome thymus, a possible contributor to an autoimmune phenotype.
- 2014
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 193:5, s. 2187-95
-
Tidskriftsartikel (refereegranskat)abstract
- Down syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall's corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes.
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| 46. |
- Skogberg, Gabriel, et al.
(författare)
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Characterization of Human Thymic Exosomes
- 2013
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nanosized membrane-bound vesicles that are released by various cell types and are capable of carrying proteins, lipids and RNAs which can be delivered to recipient cells. Exosomes play a role in intercellular communication and have been described to mediate immunologic information. In this article we report the first isolation and characterization of exosomes from human thymic tissue. Using electron microscopy, particle size determination, density gradient measurement, flow cytometry, proteomic analysis and microRNA profiling we describe the morphology, size, density, protein composition and microRNA content of human thymic exosomes. The thymic exosomes share characteristics with previously described exosomes such as antigen presentation molecules, but they also exhibit thymus specific features regarding surface markers, protein content and microRNA profile. Interestingly, thymic exosomes carry proteins that have a tissue restricted expression in the periphery which may suggest a role in T cell selection and the induction of central tolerance. We speculate that thymic exosomes may provide the means for intercellular information exchange necessary for negative selection and regulatory T cell formation of the developing thymocytes within the human thymic medulla.
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| 47. |
- Skogberg, Gabriel, et al.
(författare)
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Exosomes in the Thymus: Antigen Transfer and Vesicles.
- 2015
-
Ingår i: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Thymocytes go through several steps of maturation and selection in the thymus in order to form a functional pool of effector T-cells and regulatory T-cells in the periphery. Close interactions between thymocytes, thymic epithelial cells, and dendritic cells are of vital importance for the maturation, selection, and lineage decision of the thymocytes. One important question that is still unanswered is how a relatively small epithelial cell population can present a vast array of self-antigens to the manifold larger population of developing thymocytes in this selection process. Here, we review and discuss the literature concerning antigen transfer from epithelial cells with a focus on exosomes. Exosomes are nano-sized vesicles released from a cell into the extracellular space. These vesicles can carry proteins, microRNAs, and mRNAs between cells and are thus able to participate in intercellular communication. Exosomes have been shown to be produced by thymic epithelial cells and to carry tissue-restricted antigens and MHC molecules, which may enable them to participate in the thymocyte selection process.
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| 48. |
- Skogberg, Gabriel, et al.
(författare)
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Human thymic epithelial primary cells produce exosomes carrying tissue-restricted antigens.
- 2015
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Ingår i: Immunology and cell biology. - : Wiley. - 1440-1711 .- 0818-9641. ; 93, s. 727-73
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nano-sized vesicles released by cells into the extracellular space and have been shown to be present in thymic tissue both in mice and in humans. The source of thymic exosomes is however still an enigma and hence it is not known whether thymic epithelial cells (TECs) are able to produce exosomes. In this work, we have cultured human TECs and isolated exosomes. These exosomes carry tissue-restricted antigens (TRAs), for example, myelin basic protein and desmoglein 3. The presence of TRAs indicates a possible role for thymic epithelium-derived exosomes in the selection process of thymocytes. The key contribution of these exosomes could be to disseminate self-antigens from the thymic epithelia, thus making them more accessible to the pool of maturing thymocytes. This would increase the coverage of TRAs within the thymus, and facilitate the process of positive and negative selection.Immunology and Cell Biology advance online publication, 17 March 2015; doi:10.1038/icb.2015.33.
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| 49. |
- Wahlgren, Jessica, 1975, et al.
(författare)
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Activated Human T Cells Secrete Exosomes That Participate in IL-2 Mediated Immune Response Signaling.
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:0049723
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Tidskriftsartikel (refereegranskat)abstract
- It has previously been shown that nano-meter sized vesicles (30–100 nm), exosomes, secreted by antigen presenting cells can induce T cell responses thus showing the potential of exosomes to be used as immunological tools. Additionally, activated CD3+ T cells can secrete exosomes that have the ability to modulate different immunological responses. Here, we investigated what effects exosomes originating from activated CD3+ T cells have on resting CD3+ T cells by studying T cell proliferation, cytokine production and by performing T cell and exosome phenotype characterization. Human exosomes were generated in vitro following CD3+ T cell stimulation with anti-CD28, anti-CD3 and IL-2. Our results show that exosomes purified from stimulated CD3+ T cells together with IL-2 were able to generate proliferation in autologous resting CD3+ T cells. The CD3+ T cells stimulated with exosomes together with IL-2 had a higher proportion of CD8+ T cells and had a different cytokine profile compared to controls. These results indicate that activated CD3+ T cells communicate with resting autologous T cells via exosomes.
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- Wahlgren, Jessica, 1975, et al.
(författare)
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Delivery of Small Interfering RNAs to Cells via Exosomes
- 2016
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer New York. - 1064-3745. ; 1364, s. 105-25
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Tidskriftsartikel (refereegranskat)abstract
- Exosomes are small membrane bound vesicles between 30 and 100 nm in diameter of endocytic origin that are secreted into the extracellular environment by many different cell types. Exosomes play a role in intercellular communication by transferring proteins, lipids, and RNAs to recipient cells.Exosomes from human cells could be used as vectors to provide cells with therapeutic RNAs. Here we describe how exogenous small interfering RNAs may successfully be introduced into various kinds of human exosomes using electroporation and subsequently delivered to recipient cells. Methods used to confirm the presence of siRNA inside exosomes and cells are presented, such as flow cytometry, confocal microscopy, and Northern blot.
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