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- Title
Stimulation of CD25<sup>+</sup>CD4<sup>+</sup> regulatory T cells through GITR breaks immunological self-tolerance.
- Authors
Shimizu, Jun; Yamazaki, Sayuri; Takahashi, Takeshi; Ishida, Yasumasa; Sakaguchi, Shimon
- Abstract
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 naïve 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.
- Publication
Nature Immunology, 2002, Vol 3, Issue 2, p135
- ISSN
1529-2908
- Publication type
Academic Journal
- DOI
10.1038/ni759