Definition of target antigens for naturally occurring CD4(+) CD25(+) regulatory T cells |
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Authors: | Nishikawa Hiroyoshi Kato Takuma Tawara Isao Saito Kanako Ikeda Hiroaki Kuribayashi Kagemasa Allen Paul M Schreiber Robert D Sakaguchi Shimon Old Lloyd J Shiku Hiroshi |
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Institution: | Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan. |
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Abstract: | The antigenic targets recognized by naturally occurring CD4+ CD25+ regulatory T cells (T reg cells) have been elusive. We have serologically defined a series of broadly expressed self-antigens derived from chemically induced mouse sarcomas by serological identification of antigens by recombinant expression cloning (SEREX). CD4+ CD25+ T cells from mice immunized with SEREX-defined self-antigens had strong suppressive activity on peptide-specific proliferation of CD4+ CD25− T cells and CD8+ T cells. The suppressive effect was observed without in vitro T cell stimulation. Foxp3 expression in these CD4+ CD25+ T cells from immunized mice was 5–10 times greater than CD4+ CD25+ T cells derived from naive mice. The suppressive effect required cellular contact and was blocked by anti-glucocorticoid–induced tumor necrosis factor receptor family–related gene antibody. In vitro suppressive activity essentially disappeared 8 wk after the last immunization. However, it was regained by in vitro restimulation with cognate self-antigen protein but not with control protein. We propose that SEREX-defined self-antigens such as those used in this study represent self-antigens that elicit naturally occurring CD4+ CD25+ T reg cells. |
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