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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Shimizu J,Yamazaki S,Takahashi T,Ishida Y,Sakaguchi S

doi

10.1038/ni759

keywords:

subject

Has Abstract

pub_date

2002-02-01 00:00:00

pages

135-42

issue

2

eissn

1529-2908

issn

1529-2916

pii

ni759

journal_volume

3

pub_type

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