Absence of CD4+CD25+ regulatory T cells is associated with a loss of regulation leading to increased pathology in Helicobacter pylori-infected mice |
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| Authors: | Raghavan S Fredriksson M Svennerholm A-M Holmgren J Suri-Payer E |
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| Affiliation: | Department of Medical Microbiology and Immunology, G?teborg University, G?teborg, Sweden. sukanya.raghavan@microbio.gu.se |
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| Abstract: | Helicobacter pylori induces symptomatic chronic gastritis in a subpopulation of infected individuals. The mechanism(s) determining the development and severity of pathology leading to symptoms are not fully understood. In a mouse model of H. pylori infection we analysed the influence of immunoregulatory CD4+CD25+ T cells on H. pylori colonization and gastritis. Athymic C57BL/6 nu/nu mice were reconstituted with (a) lymph node (LN) cells (b) LN cells depleted of CD25+ T cells (CD25(-) LN) or (c) not reconstituted at all. Mice were then infected orally with 3 x 10(8)H. pylori SS1 bacteria. At 2 and 6 weeks after the inoculation there was a significant (P < 0.001) reduction in H. pylori colonization in athymic mice transferred with CD25(-) LN cells compared to mice transferred with LN cells. Colonization was still reduced at 12 weeks after inoculation. Mice transferred with CD25(-) LN cells showed an earlier onset and increased severity of gastritis as compared to mice receiving LN cells. Splenic cells isolated from mice receiving CD25(-) LN cells produced the highest level of IFN-gamma on stimulation with H. pylori antigens in vitro, had a higher H. pylori-specific DTH response and increased infiltration of CD4+ T cells and macrophages in the gastric mucosa. Athymic mice not transferred with T cells had persistent high H. pylori colonization and displayed a normal gastric epithelium without inflammatory cells. In conclusion, CD4+CD25+ cells reduce immunopathology in H. pylori infection, possibly by reducing the activation of IFN-gamma producing CD4+ T cells, even at the expense of a higher H. pylori load in the gastric mucosa. |
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| Keywords: | CD25+ regulatory T cells Helicobacter pylori mouse model gastritis |
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