Stimulation of CD25+CD4+regulatory T cells through GITR breaks immunological self-tolerance

被引：1396

作者：

Shimizu, J

Yamazaki, S

Takahashi, T

Ishida, Y

Sakaguchi, S ^{[1
]}

机构：

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

[2] Tokyo Metropolitan Inst Gerontol, Dept Immunopathol, Tokyo 1730015, Japan

[3] Nara Inst Sci & Technol, Grad Sch Biol Sci, Nara 6300101, Japan

来源：

NATURE IMMUNOLOGY | 2002年 / 3卷 / 02期

基金：

日本学术振兴会;

关键词：

D O I：

10.1038/ni759

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)-a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gene superfamily-is predominantly expressed on CD25(+)CD4(+) T cells and on CD25(+)CD4(+)CD8(-) thymocytes in normal naive mice. We found that stimulation of GITR abrogated CD25(+)CD4(+) T cell-mediated suppression. In addition, removal of GITR-expressing T cells or administration of a monoclonal antibody to GITR produced organ-specific autoimmune disease in otherwise normal mice. Thus, GITR plays a key role in dominant immunological self-tolerance maintained by CD25(+)CD4(+) regulatory T cells and could be a suitable molecular target for preventing or treating autoimmune disease.

引用

页码：135 / 142

页数：8

共 43 条

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