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Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) areessential for maintaining immunological self-tolerance and immunehomeostasis. Here, we show that a specific deficiency of cytotoxicT lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneousdevelopment of systemic lymphoproliferation, fatal T cell–mediatedautoimmune disease, and hyperproduction of immunoglobulin Ein mice, and it also produces potent tumor immunity. Treg-specificCTLA-4 deficiency impairs in vivo and in vitro suppressive functionof Tregs—in particular, Treg-mediated down-regulationof CD80 and CD86 expression on dendritic cells. Thus, naturalTregs may critically require CTLA-4 to suppress immune responsesby affecting the potency of antigen-presenting cells to activateother T cells.
1 Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. 2 Department of Rheumatology and Haematology, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan. 3 Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan. 4 Laboratory of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.
* Present address: Department of Medical Inflammation Research,Karolinska Institute, Stockholm 17177, Sweden.
To whom correspondence should be addressed. E-mail: shimon{at}frontier.kyoto-u.ac.jp
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