CTLA-4 control over Foxp3+ regulatory T cell function

被引：2311

作者：

Wing, Kajsa ^{[1
]}

Onishi, Yasushi ^{[1
,2
]}

Prieto-Martin, Paz ^{[1
]}

Yamaguchi, Tomoyuki ^{[1
]}

Miyara, Makoto ^{[1
]}

Fehervari, Zoltan ^{[1
]}

Nomura, Takashi ^{[1
]}

Sakaguchi, Shimon ^{[1
,3
,4
]}

机构：

[1] Kyoto Univ, Dept Expt Pathol, Inst Frontier Med Sci, Kyoto 6068507, Japan

[2] Tohoku Univ, Grad Sch Med, Dept Rheumatol & Haematol, Sendai, Miyagi 9808574, Japan

[3] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan

[4] Osaka Univ, Expt Immunol Lab, World Premier Int Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan

来源：

SCIENCE | 2008年 / 322卷 / 5899期

基金：

日本科学技术振兴机构; 日本学术振兴会;

关键词：

D O I：

10.1126/science.1160062

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Naturally occurring Foxp3(+)CD4(+) regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs - in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.

引用

页码：271 / 275

页数：5

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