Definition of target antigens for naturally occurring CD4+ CD25+ regulatory T cells

Hiroyoshi Nishikawa, Takuma Kato, Isao Tawara, Kanako Saito, Hiroaki Ikeda, Kagemasa Kuribayashi, Paul M. Allen, Robert D. Schreiber, Shimon Sakaguchi, Lloyd J. Old, Hiroshi Shiku

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


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.

Original languageEnglish
Pages (from-to)681-686
Number of pages6
JournalJournal of Experimental Medicine
Issue number5
StatePublished - Mar 7 2005


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