The Journal of Experimental Medicine
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Published 7 March 2005. doi:10.1084/jem.20041959
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 681-686
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BRIEF DEFINITIVE REPORT

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

Hiroyoshi Nishikawa1, Takuma Kato2, Isao Tawara1, Kanako Saito1,2, Hiroaki Ikeda1,3, Kagemasa Kuribayashi2, Paul M. Allen3, Robert D. Schreiber3, Shimon Sakaguchi4, Lloyd J. Old5, and Hiroshi Shiku1

1 Second Department of Internal Medicine, Mie University School of Medicine, Mie 514-8507, Japan
2 Department of Bioregulation, Mie University School of Medicine, Mie 514-8507, Japan
3 Department of Pathology and Immunology, Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110
4 Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8507, Japan
5 Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

CORRESPONDENCE Hiroshi Shiku: shiku{at}clin.medic.mie-u.ac.jp

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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