| 1. |
- Azem, Josef, 1961, et al.
(författare)
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B cells pulsed with Helicobacter pylori antigen efficiently activate memory CD8+ T cells from H. pylori-infected individuals
- 2005
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Ingår i: Clin Immunol. - : Elsevier BV. ; 118:2-3, s. 284-91
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori infection causes chronic gastritis that may progress to peptic ulcers or gastric adenocarcinoma and thereby cause major world-wide health problems. Previous studies have shown that CD4+ T cells are important in the immune response to H. pylori in humans, but the role of CD8+ T cells is less clear. In order to study the CD8+ T cell response to H. pylori in greater detail, we have evaluated efficient conditions for activation of CD8+ T cells in vitro. We show that H. pylori-reactive CD8+ T cells can be activated most efficiently by B cells or dendritic cells pulsed with H. pylori antigens. We further show that the majority of CD8+ T cells in H. pylori-infected gastric mucosa are memory cells, and that memory CD8+ T cells sorted from peripheral blood of H. pylori-infected individuals respond 15-fold more to H. pylori urease compared to memory cells from uninfected subjects. We conclude that CD8+ T cells do participate in the immune response to H. pylori, and this may have implications for the development of more severe disease outcomes in H. pylori-infected subjects.
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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. |
- Bjersing, Jan, 1966, et al.
(författare)
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Synergistic action of immunostimulatory DNA and fcgamma receptor IIB-crosslinking on B-cell phenotype and function
- 2005
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 210:1, s. 23-32
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Tidskriftsartikel (refereegranskat)abstract
- CpG DNA functions via the toll-like receptor-9 (TLR-9) receptor, inducing B cell proliferation and promoting immunoglobulin production. B cell responses to CpG DNA-containing immune complexes could be important in chronic autoimmunity and immune responses to bacterial components. Therefore, we investigated the potential synergy of CpG DNA-stimulation with FcgammaR clustering (CFR) on splenic B cell activity. CFR-induced splenocyte proliferation was significantly increased compared to treatment with CpG DNA alone. While the levels of interleukin-10 (IL-10) were increased in CpG DNA-treated splenocyte cultures, particularly following FcgammaRII/III-clustering, CFR treatment reduced IL-6 levels. B-cell maturation in culture was enhanced by CFR. Indeed, the frequency of IgG expressing cells after stimulation with CpG DNA was increased and was even higher after CFR stimulation. Furthermore, the frequency of plasma cell precursors was markedly increased by stimulation with CFR. Late splenic B cell subsets, transitional type 2 (T2) and mature (M) B cells, responded strongly to CpG DNA with proliferation and the response was enhanced by FcgammaR-clustering. Immature transitional type 1 (T1) B cells showed distinctly lower proliferative response to CpG DNA and very small effects of FcgammaR-clustering, despite similar expression of Fcgamma-receptors by all B cell subsets. In conclusion, these data show synergistic impact of CpG DNA and simultaneous FcgammaR-clustering on B cell proliferation and differentiation.
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| 4. |
- Brisslert, Mikael, 1974, et al.
(författare)
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Helicobacter pylori induce neutrophil transendothelial migration: role of the bacterial HP-NAP
- 2005
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Ingår i: FEMS Microbiol Lett. ; 249:1, s. 95-103
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Tidskriftsartikel (refereegranskat)abstract
- Continuous recruitment of neutrophils into the inflamed gastric mucosal tissue is a hallmark of Helicobacter pylori infection in humans. In this study, we examined the ability of H. pylori to induce transendothelial migration of neutrophils using a transwell system consisting of a cultured monolayer of human endothelial cells as barrier between two chambers. We showed for the first time that live H. pylori, but not formalin-killed bacteria, induced a significantly increased transendothelial migration of neutrophils. H. pylori conditioned culture medium also induced significantly increased transendothelial migration, whereas heat-inactivated culture filtrates had no effect, suggesting that the chemotactic factor was proteinaceous. Depletion of H. pylori-neutrophil activating protein (HP-NAP) from the culture filtrates resulted in significant reduction of the transmigration. Culture filtrates from isogenic HP-NAP deficient mutant bacteria also induced significantly less neutrophil migration than culture filtrates obtained from wild-type bacteria. HP-NAP did not induce endothelial cell activation, suggesting that HP-NAP acts directly on the neutrophils. In conclusion, our results demonstrate that secreted HP-NAP is one of the factors resulting in H. pylori induced neutrophil transendothelial migration. We propose that HP-NAP contributes to the continuous recruitment of neutrophils to the gastric mucosa of H. pylori infected individuals.
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| 5. |
- Ellmark, Peter, et al.
(författare)
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Identification of protein expression signatures associated with Helicobacter pylori infection and gastric adenocarcinoma using recombinant antibody microarrays.
- 2006
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Ingår i: Molecular & cellular proteomics : MCP. - 1535-9476 .- 1535-9484. ; 5:9, s. 1638-46
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Tidskriftsartikel (refereegranskat)abstract
- Antibody microarray based technology is a powerful emerging tool in proteomics, target discovery, and differential analysis. Here, we report the first study where recombinant antibody fragments have been used to construct large scale antibody microarrays, composed of 127 different antibodies against mostly immunoregulatory antigens. The arrays were based on single framework recombinant antibody fragments (SinFabs) designed for high on-chip stability and functionality and were used for the analysis of malignant and normal stomach tissue samples from Helicobacter pylori-positive and -negative patients. Our results demonstrate that distinct tumor- as well as infection-associated protein expression signatures could be identified from these complex tissue proteomes, as well as biomarkers such as IL-9, IL-11, and MCP-4, previously not found in these diseases. In a longer perspective, this study may improve the understanding of H. pylori-induced stomach cancer and lead to development of improved diagnostics.
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| 9. |
- Enarsson, Karin, 1975, et al.
(författare)
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CD4+ CD25high regulatory T cells reduce T cell transendothelial migration in cancer patients.
- 2007
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Ingår i: European journal of immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 37:1, s. 282-91
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Tidskriftsartikel (refereegranskat)abstract
- Cell-mediated immunity is thought to be the main mechanism of anti-tumour responses of the host, but it is not known if cancer disease affects T cell recruitment from blood to tissues. Therefore, we compared Heliobacter pylori-induced T cell transendothelial migration (TEM) in H. pylori-infected gastric carcinoma patients, colon and lung carcinoma patients and healthy volunteers. H. pylori induced significant T cell migration from all groups. However, there was a dramatic reduction of T cell TEM in gastric carcinoma patients (80%) compared to healthy individuals. A similarly reduced transmigration was also seen in colon and lung carcinoma patients. We found significantly increased frequencies of T(reg) cells in the blood of gastric carcinoma patients compared to healthy individuals, and depletion of T(reg) cells from the blood of these patients prior to TEM restored T cell migration. The effect of T(reg) cells was largely dependent on cell-cell contact, but not on IL-10 or TGF-beta. In addition, the presence of T(reg) cells led to reduced T cell attachment to endothelium and decreased production of T cell-recruiting chemokines during TEM. In conclusion, T(reg) cell-mediated reduction of T cell TEM may reduce T cell recruitment in patients with epithelial malignancies, thereby hampering anti-tumour responses.
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| 10. |
- 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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