| 1. |
- Fergusson, J. R., et al.
(författare)
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CD161(int)CD8+T cells : a novel population of highly functional, memory CD8+T cells enriched within the gut
- 2016
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Ingår i: Mucosal Immunology. - : Elsevier BV. - 1933-0219 .- 1935-3456. ; 9:2, s. 401-413
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Tidskriftsartikel (refereegranskat)abstract
- The C-type lectin-like receptor CD161 is expressed by lymphocytes found in human gut and liver, as well as blood, especially natural killer (NK) cells, T helper 17 (Th17) cells, and a population of unconventional Tcells known as mucosalassociated invariant T (MAIT) cells. The association of high CD161 expression with innate T-cell populations including MAITcells is established. Here we show that CD161 is also expressed, at intermediate levels, on a prominent subset of polyclonal CD8+ T cells, including antiviral populations that display a memory phenotype. These memory CD161(int)CD8+ Tcells are enriched within the colon and express both CD103 and CD69, markers associated with tissue residence. Furthermore, this population was characterized by enhanced polyfunctionality, increased levels of cytotoxic mediators, and high expression of the transcription factors T-bet and eomesodermin (EOMES). Such populations were induced by novel vaccine strategies based on adenoviral vectors, currently in trial against hepatitis C virus. Thus, intermediate CD161 expression marks potent polyclonal, polyfunctional tissue-homing CD8+ T-cell populations in humans. As induction of such responses represents a major aim of T-cell prophylactic and therapeutic vaccines in viral disease and cancer, analysis of these populations could be of value in the future.
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| 2. |
- Fergusson, Joannah R., et al.
(författare)
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CD161 Defines a Transcriptional and Functional Phenotype across Distinct Human T Cell Lineages
- 2014
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 9:3, s. 1075-1088
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Tidskriftsartikel (refereegranskat)abstract
- The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCR gamma delta+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage.
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| 3. |
- Sverremark-Ekström, E., et al.
(författare)
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Peanut sensitization during the first 5yr of life is associated with elevated levels of peanut-specific IgG
- 2012
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 23, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergen-specific IgE antibodies are implicated in allergic diseases while allergen-specific IgG antibodies have been proposed to prevent allergic reactions. The objective for this study was to study whether the immune response (IgG and IgG4) to peanut differs in IgE-sensitized and non-sensitized young children. Methods: A total of 239 children have been followed prospectively from birth to 5yr of age. The levels of IgG and IgG4 to peanut, Ara h 2, and Ara h 8 were analyzed at 2 and 5yr of age and related to IgE sensitization and peanut consumption. Results: The levels of peanut-specific IgG and IgG4 were significantly higher in peanut-sensitized children at 2 and 5yr of age when compared with non-sensitized children and children sensitized to other food/inhalant allergens. A strong correlation was seen between levels of peanut-specific IgG/IgG4-ratios and peanut-specific IgE at 5yr of age. Children avoiding peanuts, a subgroup of the peanut sensitized, had statistically significant higher levels of IgE to peanut and a tendency of higher IgG and IgG4 levels to peanut. In the avoidance group, significant correlations between IgE and IgG/IgG4 to peanut were found compared with children eating peanuts. Conclusion: Peanut-specific IgG or IgG4 levels were elevated in peanut-sensitized children especially those avoiding peanuts. In our study, IgG and IgG4 do not seem to indicate tolerance or protection from sensitization. © 2012 John Wiley & Sons A/S.
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| 4. |
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| 5. |
- Holmlund, U., et al.
(författare)
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Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring
- 2010
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Ingår i: Clinical and Experimental Immunology. - Oxford, Untited Kingdom : Wiley-Blackwell Publishing Inc.. - 0009-9104 .- 1365-2249. ; 162:3, s. 500-509
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Tidskriftsartikel (refereegranskat)abstract
- Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0 center dot 034) and CXCL-8/IL-8 (P = 0 center dot 037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-beta 1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses.
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| 6. |
- Kurioka, Ayako, et al.
(författare)
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Shared and Distinct Phenotypes and Functions of Human CD161++ V alpha 7.2+T Cell Subsets
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Human mucosal-associated invariant T (MAIT) cells are an important T cell subset that are enriched in tissues and possess potent effector functions. Typically such cells are marked by their expression of V alpha 7.2-J alpha 33/J alpha 20/J alpha 12 T cell receptors, and functionally they are major histocompatibility complex class I-related protein 1 (MR1)-restricted, responding to bacterially derived riboflavin synthesis intermediates. MAIT cells are contained within the CD161++ V alpha 7.2+ T cell population, the majority of which express the CD8 receptor (CD8+), while a smaller fraction expresses neither CD8 or CD4 coreceptor (double negative; DN) and a further minority are CD4+. Whether these cells have distinct homing patterns, phenotype and functions have not been examined in detail. We used a combination of phenotypic staining and functional assays to address the similarities and differences between these CD161++ V alpha 7.2+ T cell subsets. We find that most features are shared between CD8+ and DN CD161++ V alpha 7.2+ T cells, with a small but detectable role evident for CD8 binding in tuning functional responsiveness. By contrast, the CD4+ CD161++ V alpha 7.2+ T cell population, although showing MR1-dependent responsiveness to bacterial stimuli, display reduced T helper 1 effector functions, including cytolytic machinery, while retaining the capacity to secrete interleukin-4 (IL-4) and IL-13. This was consistent with underlying changes in transcription factor (TF) expression. Although we found that only a proportion of CD4+ CD161++ V alpha 7.2+ T cells stained for the MR1-tetramer, explaining some of the heterogeneity of CD4+ CD161++ V alpha 7.2+ T cells, these differences in TF expression were shared with CD4+ CD161++ MR1-tetramer+ cells. These data reveal the functional diversity of human CD161++ V alpha 7.2+ T cells and indicate potentially distinct roles for the different subsets in vivo.
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| 7. |
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| 8. |
- Sjögren, Y M, et al.
(författare)
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Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses
- 2009
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 39:12, s. 1842-1851
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs).Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex.Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
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| 9. |
- Stone, Virginia M., et al.
(författare)
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Inhibition of Type III Interferon Expression in Intestinal Epithelial Cells-A Strategy Used by Coxsackie B Virus to Evade the Host's Innate Immune Response at the Primary Site of Infection?
- 2021
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Increasing evidence highlights the importance of the antiviral activities of the type III interferons (IFN lambda s; IL-28A, IL-28B, IL29, and IFN lambda 4) in the intestine. However, many viruses have developed strategies to counteract these defense mechanisms by preventing the production of IFNs. Here we use infection models, a clinical virus isolate, and several molecular biology techniques to demonstrate that both type I and III IFNs induce an antiviral state and attenuate Coxsackievirus group B (CVB) replication in human intestinal epithelial cells (IECs). While treatment of IECs with a viral mimic (poly (I:C)) induced a robust expression of both type I and III IFNs, no such up-regulation was observed after CVB infection. The blunted IFN response was paralleled by a reduction in the abundance of proteins involved in the induction of interferon gene transcription, including TIR-domain-containing adapter-inducing interferon-beta (TRIF), mitochondrial antiviral-signaling protein (MAVS), and the global protein translation initiator eukaryotic translation initiation factor 4G (eIF4G). Taken together, this study highlights a potent anti-Coxsackieviral effect of both type I and III IFNs in cells located at the primary site of infection. Furthermore, we show for the first time that the production of type I and III IFNs in IECs is blocked by CVBs. These findings suggest that CVBs evade the host immune response in order to successfully infect the intestine.
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| 10. |
- Sverremark-Ekström, Eva, et al.
(författare)
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Peanut sensitization during the first five years of life is associated with elevated levels of peanut-specific IgG
- 2012
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 23:3, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergen-specific IgE antibodies are implicated in allergic diseases while allergen-specific IgG antibodies have been proposed to prevent allergic reactions. The objective for this study was to study if the immune response (IgG and IgG4) to peanut differs in IgE sensitized and non-sensitized young children.Methods: A total of 239 children have been followed prospectively from birth to 5 years of age. Levels of IgG and IgG4 to peanut, Ara h 2 and Ara h 8 were analyzed at 2 and 5 years of age and related to IgE-sensitization and peanut consumption.Results: Levels of peanut-specific IgG and IgG4 were significantly higher in peanut-sensitized children at 2 and 5 years of age when compared to non-sensitized children and children sensitized to other food/inhalant allergens. A strong correlation was seen between levels of peanut-specific IgG/IgG4-ratios and peanut-specific IgE at 5 years of age. Children avoiding peanuts, a subgroup of the peanut sensitized, had statistically significant higher levels of IgE to peanut and a tendency of higher IgG and IgG4 levels to peanut. In the avoidance-group significant correlations between IgE and IgG/IgG4 to peanut was found compared to children eating peanuts. Conclusion: Peanut-specific IgG or IgG4 levels were elevated in peanut-sensitized children especially those avoiding peanuts. In our study, IgG and IgG4 do not seem to indicate tolerance or protection from sensitization.
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