TY  - JOUR
AU  - Zwar, TA
AU  - Read, S
AU  - van Driel, IR
AU  - Gleeson, PA
Y2  - 2014/05/21
Y1  - 2006/02/01
SN  - 0022-1767
UR  - http://hdl.handle.net/11343/26621
AB  - 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.
N1  - application/pdf
LA  - English
PB  - AMER ASSOC IMMUNOLOGISTS
KW  - Biochemistry and Cell Biology not elsewhere classified ; Biological Sciences
T1  - CD4(+)CD25(+) regulatory T cells inhibit the antigen-dependent expansion of self-reactive T cells in vivo
DO  - 10.4049/jimmunol.176.3.1609
IS  - JOURNAL OF IMMUNOLOGY
VL  - 176
IS  - 3
SP  - 1609-1617
L1  - /bitstream/handle/11343/26621/116836_5475.pdf?sequence=1&isAllowed=n
ER  -