CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms

被引：140

作者：

Ise, Wataru ^{[1
,2
]}

Kohyama, Masako ^{[1
,2
]}

Nutsch, Katherine M. ^{[1
]}

Lee, Hyang Mi ^{[1
]}

Suri, Anish ^{[1
]}

Unanue, Emil R. ^{[1
]}

Murphy, Theresa L. ^{[1
]}

Murphy, Kenneth M. ^{[1
,2
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA

[2] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 02期

基金：

美国国家卫生研究院;

关键词：

CUTTING EDGE; IN-VITRO; ACTIVATION; ABSENCE; LYMPHOCYTE; ENGAGEMENT; TOLERANCE; CD28; HOMEOSTASIS; DEFICIENT;

D O I：

10.1038/ni.1835

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The inhibitory immunoregulatory receptor CTLA-4 is critical in maintaining self-tolerance, but the mechanisms of its actions have remained controversial. Here we examined the antigen specificity of tissue-infiltrating CD4(+) T cells in Ctla4(-/-) mice. After adoptive transfer, T cells isolated from tissues of Ctla4(-/-) mice showed T cell antigen receptor (TCR)-dependent accumulation in the tissues from which they were derived, which suggested reactivity to tissue-specific antigens. We identified the pancreas-specific enzyme PDIA2 as an autoantigen in Ctla4(-/-) mice. CTLA-4 expressed either on PDIA2-specific effector cells or on regulatory T cells was sufficient to control tissue destruction mediated by PDIA2-specific T cells. Our results demonstrate that both cell-intrinsic and non-cell-autonomous actions of CTLA-4 operate to maintain T cell tolerance to a self antigen.

引用

页码：129 / U45

页数：8

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