| 1. |
- Lundgren, Anna, 1974, et al.
(författare)
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Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients
- 2005
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Ingår i: Infect Immun. ; 73:1, s. 523-31
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori chronically colonizes the stomach and duodenum and causes peptic ulcers or gastric adenocarcinoma in 10 to 20% of infected individuals. We hypothesize that the inability of patients to clear H. pylori infections is a consequence of active suppression of the immune response. Here we show that H. pylori-infected individuals have increased frequencies of CD4(+) CD25(high) T cells in both the stomach and duodenal mucosa compared to uninfected controls. These cells have the phenotype of regulatory T cells, as they express FOXP3, a key gene for the development and function of regulatory T cells, as well as high levels of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) protein. In contrast, mucosal CD4(+) CD25(low) and CD4(+) CD25(-) cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4(+) CD25(high) T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4(+) CD25(high) cells are also increased in the stomachs of H. pylori-infected patients with gastric adenocarcinoma, particularly in cancer-affected tissues. These findings suggest that regulatory T cells may suppress mucosal immune responses and thereby contribute to the persistence of H. pylori infections.
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| 2. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Cholera caused by Vibrio cholerae O1 induces T-cell responses in the circulation.
- 2009
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Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 1888-93
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Tidskriftsartikel (refereegranskat)abstract
- Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-gamma) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4(+) T cells (CD4(+) beta7(+)), gut-homing CD8(+) T cells (CD8(+) beta7(+)), and gut-homing B cells (CD19(+) beta7(+)) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4(+) and CD8(+) T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-gamma responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-gamma) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.
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| 3. |
- Bhuiyan, Taufiqur Rahman, 1974, et al.
(författare)
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Comparison of mucosal B- and T-cell responses in Helicobacter pylori-infected subjects in a developing and a developed country.
- 2008
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Ingår i: FEMS immunology and medical microbiology. - 0928-8244. ; 54:1, s. 70-9
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori is highly endemic in developing countries, but comparatively little is known about mucosal immune responses to H. pylori in these settings. Therefore, we have compared B- and T-cell responses, with a focus on the gastrointestinal mucosa, in H. pylori-infected adults in a developing (Bangladesh) and a developed (Sweden) country. We found comparable numbers of CD19(+) B cells and CD4 (+)T cells and similar levels of H. pylori-specific IgA antibodies in gastric mucosa from Bangladeshi and Swedish volunteers. However, about threefold higher numbers of CD19(+) B cells and 12-fold increased levels of H. pylori-specific IgA antibodies were found in the duodenum of Bangladeshi subjects. The gastric and duodenal immune responses in Bangladeshi asymptomatic carriers and duodenal ulcer patients were comparable. Bangladeshi subjects had about twofold lower titers of H. pylori-specific IgA and IgG antibodies in the circulation compared with Swedish volunteers. In conclusion, our findings suggest that Bangladeshi individuals have comparable gastric immune responses, but lower systemic antibody responses to H. pylori, compared with Swedish volunteers. Increased inflammation is present in the duodenum of Bangladeshi volunteers, maybe as a result of frequent exposure to enteric infections in these individuals.
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| 4. |
- Enarsson, Karin, 1975, et al.
(författare)
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Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa
- 2006
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Ingår i: Clin Immunol. - : Elsevier BV. ; 118:1, s. 24-34
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Forskningsöversikt (refereegranskat)abstract
- Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.
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| 5. |
- Holmén, Nathalie, 1979, et al.
(författare)
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Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity.
- 2006
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Ingår i: Inflammatory bowel diseases. - 1078-0998. ; 12:6, s. 447-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Factors determining the extension and degree of inflammation in the colonic mucosa of patients with ulcerative colitis (UC) are largely unknown, but CD4+CD25high regulatory T cells (Tregs) have been implicated to play an important role in suppressing inflammation. Therefore, the aims of this study were to determine whether colonic Tregs have suppressive effects on colonic effector T cells in UC and to analyze the association between segmental colonic Treg distribution and disease activity. MATERIALS AND METHODS: The suppressive activity of colonic CD4+CD25high Tregs from patients with active UC was determined in coculture assays measuring proliferation and cytokine production. The frequency of Tregs and the expression of the Treg marker FOXP3 were analyzed with flow cytometry and RT-PCR in isolated cells and the whole mucosa from patients with active and inactive disease, as well as healthy mucosa. RESULTS: Colonic CD4+CD25high T cells from patients with UC suppressed the proliferation and cytokine secretion of colonic effector CD4+ T cells. Healthy controls but not patients with UC had lower Treg frequencies in the sigmoid than in the ascending colon. Patients with UC with active disease had increased frequency of colonic Tregs. The frequency of Tregs was positively correlated with colonic disease activity and serum C-reactive protein. CONCLUSIONS: Colonic CD4+CD25high Tregs are able to suppress colonic effector T cell activity in vitro, and the Treg frequency in the inflamed intestine increases with disease activity in patients with active UC. This suggests that Tregs may be outnumbered by other inflammatory cells or that their suppressive activity may be influenced by the in vivo environment.
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| 6. |
- Janzon, Anders, 1978, et al.
(författare)
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Presence of high numbers of transcriptionally active Helicobacter pylori in vomitus from Bangladeshi patients suffering from acute gastroenteritis.
- 2009
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Ingår i: Helicobacter. - : Wiley. - 1523-5378 .- 1083-4389. ; 14:4, s. 237-47
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Helicobacter pylori is one of the most prevalent human bacterial pathogens; however, its transmission pathways remain unknown. New infections of H. pylori during outbreaks of gastroenteritis have been suggested previously, and to explore this transmission route further H. pylori was quantified in vomitus and diarrheal stool of patients suffering from acute gastroenteritis in Dhaka, Bangladesh. MATERIALS AND METHODS: Vomitus and stool samples from 28 patients seeking care at the International Centre for Diarrhoeal Disease Research hospital were analyzed for presence of H. pylori and other pathogens using quantitative culturing, real-time polymerase chain reaction (PCR), and H. pylori stool antigen test. Bacterial gene expression was analyzed using reverse transcriptase real-time PCR. RESULTS: The results of real-time PCR show that 23 (88%) of the 26 vomitus samples and 17 (74%) of the 23 stool samples were H. pylori positive, while stool antigen test show that 14 (67%) of the 21 stool samples were H. pylori positive. H. pylori could not be isolated by culture. Analysis using quantitative culture and real-time PCR to detect Vibrio cholerae showed strong correlation between these methods, and validating real-time PCR. Analysis of H. pylori virulence gene transcription in vomitus, diarrheal stool, antral and duodenal biopsy specimens, and in vitro cultures showed that cagA, flaA, and ureA were highly transcribed in vomitus, biopsy specimens, and cultures, whereas hpaA and vacA were expressed at lower levels. No H. pylori gene expression was detected in diarrheal stool. CONCLUSIONS: We conclude that high numbers of transcriptionally active H. pylori are shed in vomitus, which indicates that new infections may be disseminated through vomiting.
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| 7. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation.
- 2009
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Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 28:2, s. 422-9
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Tidskriftsartikel (refereegranskat)abstract
- Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral((R)) containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10-18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P<0.01) and IFN-gamma production (P<0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P>0.05). The IFN-gamma production was significantly higher (P<0.01) but the blast formation comparable (P>0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P<0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-gamma as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.
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| 8. |
- Ahmed, Tanvir, 1970, et al.
(författare)
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Children with the Le(a+b-) blood group have increased susceptibility to diarrhea caused by enterotoxigenic Escherichia coli expressing colonization factor I group fimbriae.
- 2009
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Ingår i: Infection and immunity. - 1098-5522. ; 77:5, s. 2059-64
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies have shown that children with blood group A have increased susceptibility to enterotoxigenic Escherichia coli (ETEC) diarrhea and that Lewis blood group "a" antigen (Le(a)) may be a candidate receptor for ETEC colonization factor (CF) antigen I (CFA/I) fimbriae. Based on these findings, we have attempted to determine if children with the Le(a+b-) phenotype may be more susceptible to diarrhea caused by ETEC, in particular ETEC expressing CFA/I and related fimbriae of the CFA/I group, than Le(a-b+) children. To test this hypothesis, we have determined the Lewis antigen expression in 179 Bangladeshi children from a prospective birth cohort study in urban Dhaka in which ETEC expressing major CFs such as CFA/I, CS3, CS5, and CS6 was the most commonly isolated diarrhea pathogen during the first 2 years of life. The Lewis blood group phenotypes were determined by a dot blot immunoassay using saliva samples and by a tube agglutination test using fresh red blood cells. The results indicate that Le(a+b-) children more often had symptomatic than asymptomatic ETEC infections (P < 0.001), whereas symptomatic and asymptomatic ETEC infections were equally frequent in Le(a-b+) children. We also show that children with the Le(a+b-) blood type had significantly higher incidences of diarrhea caused by ETEC expressing fimbriae of the CFA/I group than Le(a-b+) children (P < 0.001). In contrast, we did not find any association between the Lewis blood group phenotype and diarrhea caused by ETEC expressing CS6 or rotavirus.
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| 9. |
- Enarsson, Karin, 1975, et al.
(författare)
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Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma.
- 2006
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Ingår i: Clinical immunology (Orlando, Fla.). - : Elsevier BV. - 1521-6616. ; 121:3, s. 358-68
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Tidskriftsartikel (refereegranskat)abstract
- CD4(+)CD25(high) FOXP3-expressing regulatory T cells (Treg) can suppress immune responses to infections and tumors, thereby promoting microbial persistence and tumor progression. However, little is known about the phenotype and function of human mucosal Treg. Therefore, we analyzed the suppressive activity and homing phenotype of Treg in gastric mucosa of Helicobacter pylori-infected gastric adenocarcinoma patients. We found increased numbers of CD4(+)FOXP3(+) Treg in the tumor compared to tumor-free gastric mucosa. Gastric Treg cells were able to suppress H. pylori-induced T cell proliferation and IFN-gamma production. Furthermore, gastric Treg expressed increased levels of l-selectin and CCR4, compared to non-Treg cells, suggesting that these receptors contribute to Treg recruitment. The presence of functional antigen-specific Treg in H. pylori-infected gastric mucosa supports an important role for these cells in suppression of mucosal effector T cell responses, which probably contribute to bacterial persistence and possibly also to gastric tumor progression.
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| 10. |
- Hansson, Malin, 1967, et al.
(författare)
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Dendritic cells express CCR7 and migrate in response to CCL19 (MIP-3beta) after exposure to Helicobacter pylori
- 2006
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 8:3, s. 841-50
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Forskningsöversikt (refereegranskat)abstract
- Helicobacter pylori infection induces chronic inflammation in the gastric mucosa with a marked increase in the number of lymphoid follicles consisting of infiltrating B and T cells, neutrophils, dendritic cells (DC) and macrophages. It has been suggested that an accumulation of mature DC in the tissue, resulting from a failure of DC to migrate to lymph nodes, may contribute to this chronic inflammation. Migration of DC to lymph nodes is regulated by chemokine receptor CCR7, expressed on mature DC, and the CCR7 ligands CCL19 and CCL21. In this study we analysed the maturation, in vitro migration and cytokine production of human DC after stimulation with live H. pylori. For comparison, DC responses to non-pathogenic Escherichia coli bacteria were also evaluated. Stimulation with H. pylori induced maturation of DC, i.e. up-regulation of the chemokine receptors CCR7 and CXCR4 and the maturation markers HLA-DR, CD80 and CD86. The H. pylori-stimulated DC also induced CD4(+) T-cell proliferation. DC stimulated with H. pylori secreted significantly more interleukin (IL)-12 compared to DC stimulated with E. coli, while E. coli-stimulated DC secreted more IL-10. Despite low surface expression of CCR7 protein following stimulation with H. pylori compared to E. coli, the DC migrated equally well towards CCL19 after stimulation with both bacteria. Thus, we could not detect any failure in the migration of H. pylori stimulated DC in vitro that may contribute to chronic gastritis in vivo, and our results suggest that H. pylori induces maturation and migration of DC to lymph nodes where they promote T cell responses.
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