Downregulation of IL-12 and a novel negative feedback system mediated by CD25+CD4+ T cells |
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Authors: | Sato Kojiro Tateishi Shoko Kubo Kanae Mimura Toshihide Yamamoto Kazuhiko Kanda Hiroko |
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Affiliation: | Department of Allergy and Rheumatology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. satok-tky@umin.ac.jp |
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Abstract: | CD25(+)CD4(+) regulatory T cells suppress immune responses and are believed to play roles in preventing autoimmune diseases. However, the mechanism(s) underlying the suppression and the regulation of their homeostasis remain to be elucidated. Here we show that these regulatory T cells downregulated CD25(-)CD4(+) T-cell-mediated production of IL-12 from antigen-presenting cells, which can act as a growth factor for CD25(-)CD4(+) T cells. We further found that CD25(+)CD4(+) T cells, despite their well-documented "anergic" nature, proliferate significantly in vitro only when CD25(-)CD4(+) T cells are present. Notably, this proliferation was strongly dependent on IL-2 and relatively independent of IL-12. Thus, CD25(+)CD4(+) T cells suppress CD25(-)CD4(+) T-cell responses, at least in part, by inhibiting IL-12 production while they themselves can undergo proliferation with the mediation of CD25(-)CD4(+) T cells in vitro. These results offer a novel negative feedback system involving a tripartite interaction among CD25(+)CD4(+) and CD25(-)CD4(+) T cells, and APCs that may contribute to the termination of immune responses. |
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Keywords: | T cells Cell proliferation Suppression Anergy IL-12 IL-2 CD25 CD80 CD86 CTLA-4 |
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