| 1. |
- Johansson, Eva-Liz, et al.
(författare)
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Comparison of different routes of vaccination for eliciting antibody responses in the human stomach
- 2004
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 22:8, s. 984-90
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Tidskriftsartikel (refereegranskat)abstract
- Determination of optimal routes to induce mucosal immune responses locally in the stomach and duodenum are important steps in the development of vaccines against Helicobacter pylori infection. In this study, we immunized H. pylori-infected individuals either nasally or rectally with a model antigen, i.e. cholera toxin B subunit, and compared the immune responses after these routes with the responses after oral or intrajejunal vaccination. Specific antibody levels in serum as well as specific antibody levels and antibody-secreting cells in biopsies from antrum and duodenum were determined by ELISA and ELISPOT methods. In contrast to oral vaccination, nasal and rectal vaccination did not induce significant increases in specific antibody-secreting cells either in the antrum or duodenum. Furthermore, when analyzing the antibody levels in saponin extracted biopsies, intrajejunal vaccination was superior to both nasal and rectal vaccination in inducing antigen-specific IgA levels in the stomach. We conclude that oral vaccination is the optimal route for induction of antigen-specific IgA antibody responses in the stomach and duodenum of humans, while nasal or rectal vaccination is less suitable for this purpose.
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| 2. |
- 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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| 3. |
- Lindholm, Catharina, 1967, et al.
(författare)
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Mucosal vaccination increases endothelial expression of mucosal addressin cell adhesion molecule 1 in the human gastrointestinal tract.
- 2004
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Ingår i: Infection and immunity. - 0019-9567. ; 72:2, s. 1004-9
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Forskningsöversikt (refereegranskat)abstract
- Homing of leukocytes to various tissues is dependent on the interaction between homing receptors on leukocytes and their ligands, addressins, on endothelial cells. Mucosal immunization results in homing of antigen-specific lymphocytes back to the mucosa where they first encountered the antigen. However, it is unknown whether this homing of antigen-specific cells is mediated by an altered endothelial addressin expression after vaccination. Using different immunization routes with an oral cholera vaccine, we show that the endothelial expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) is increased in the gastric and upper small intestinal mucosae after immunization through various local routes in the upper gastrointestinal tract. In contrast, rectal immunization did not influence the levels of MAdCAM-1 in the gastric or duodenal mucosa. Furthermore, we show that MAdCAM-1 can be induced on human endothelial cells by tumor necrosis factor alpha (TNF-alpha) and gamma interferon. The vaccine component cholera toxin B subunit (CTB) increased MAdCAM-1 expression on endothelial cells in cultured human gastric explants, an effect that seemed to be mediated by TNF-alpha. In conclusion, MAdCAM-1 expression is increased in the upper gastrointestinal tract after local immunizations with a vaccine containing CTB. This strongly suggests the involvement of MAdCAM-1 in the preferential homing of mucosal lymphocytes to their original site of activation.
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