Cutting edge:: The natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression

被引:173
作者
Ji, HB
Liao, GX
Faubion, WA
Abadía-Molina, AC
Cozzo, C
Laroux, FS
Caton, A
Terhorst, C
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA
[2] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA
关键词
D O I
10.4049/jimmunol.172.10.5823
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
CD4(+)25(+) regulatory T (Treg) cells maintain immunological self-tolerance through mechanisms that are only in part understood. Previous studies suggest that the glucocorticoid-induced TNFR-related protein (GITR), which is preferentially expressed on the surface of Treg cells, potentially provides a signal that abrogates Treg suppression. In this study, we show that a soluble form of mouse GITR ligand (sGITR-L) induces GITR-dependent NF-kappaB activation and blocks in vitro suppression mediated by both resting and preactivated polyclonal and Ag- specific Treg cells. Since sGITR-L along with rIL-2 induces Proliferation of CD4(+)25(+) cells, it appears thats GITR-L can break the anergic state of Treg cells. Because sGITR-L also up-regulates IL-2 secretion by activated CD4(+)25(-) T cells, these two sGITR-L induced signals synergize to interfere with suppressor activity by CD4(+)25(+) Treg cells.
引用
收藏
页码:5823 / 5827
页数:5
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