CD4(+)CD25(+) regulatory T cells inhibit the antigen-dependent expansion of self-reactive T cells in vivo
AuthorZwar, TA; Read, S; van Driel, IR; Gleeson, PA
Source TitleJournal of Immunology
PublisherAMER ASSOC IMMUNOLOGISTS
AffiliationBiochemistry And Molecular Biology
Document TypeJournal Article
CitationsZwar, T. A., Read, S., van Driel, I. R. & Gleeson, P. A. (2006). CD4(+)CD25(+) regulatory T cells inhibit the antigen-dependent expansion of self-reactive T cells in vivo. JOURNAL OF IMMUNOLOGY, 176 (3), pp.1609-1617. https://doi.org/10.4049/jimmunol.176.3.1609.
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C1 - Journal Articles Refereed
A deficiency of CD4+CD25+ regulatory T cells (CD25+ Tregs) in lymphopenic mice can result in the onset of autoimmune gastritis. The gastric H/K ATPase alpha (H/Kalpha) and beta (H/Kbeta) subunits are the immunodominant autoantigens recognized by effector CD4+ T cells in autoimmune gastritis. The mechanism by which CD25+ Tregs suppress autoimmune gastritis in lymphopenic mice is poorly understood. To investigate the antigenic requirements for the genesis and survival of gastritis-protecting CD25+ Tregs, we analyzed mice deficient in H/Kbeta and H/Kalpha, as well as a transgenic mouse line (H/Kbeta-tsA58 Tg line 224) that lacks differentiated gastric epithelial cells. By adoptive transfer of purified T cell populations to athymic mice, we show that the CD25+ Treg population from mice deficient in either one or both of H/Kalpha and H/Kbeta, or from the H/Kbeta-tsA58 Tg line 224 mice, is equally effective in suppressing the ability of polyclonal populations of effector CD4+ T cells to induce autoimmune gastritis. Furthermore, CD25+ Tregs, from either wild-type or H/Kalpha-deficient mice, dramatically reduced the expansion of pathogenic H/Kalpha-specific TCR transgenic T cells and the induction of autoimmune gastritis in athymic recipient mice. Proliferation of H/Kalpha-specific T cells in lymphopenic hosts occurs predominantly in the paragastric lymph node and was dependent on the presence of the cognate H/Kalpha Ag. Collectively, these studies demonstrate that the gastritis-protecting CD25+ Tregs do not depend on the major gastric Ags for their thymic development or their survival in the periphery, and that CD25+ Tregs inhibit the Ag-specific expansion of pathogenic T cells in vivo.
KeywordsBiochemistry and Cell Biology not elsewhere classified ; Biological Sciences
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