4-1BB-dependent inhibition of immunosuppression by activated CD4+CD25+ T cells

被引:142
作者
Choi, BK
Bae, JS
Choi, EM
Kang, WJ
Sakaguchi, S
Vinay, DS
Kwon, BS
机构
[1] Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea
[2] Kyoto Univ, Dept Expt Pathol, Inst Frontier Med Sci, Kyoto, Japan
[3] Louisiana State Univ, Hlth Sci Ctr, Sch Med, Ctr Eye, New Orleans, LA USA
关键词
regulatory T lymphocytes; GVHD; tolerance; suppression;
D O I
10.1189/jlb.1003491
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
4-1BB (CD137) is a costimulatory molecule involved in the activation and survival of CD4, CD8, and natural killer cells. Although a great deal has been learned as to how 4-1BB-mediated signaling governs the immunity of conventional T cells, the functional role of 4-1BB in the context of CD4(+)CD25(+) regulatory T cell (Tr) activation is largely unknown. Using 4-1BB-intact and -deficient mice, we investigated the effect of the 4-1BB/4-1BB ligand pathway on the suppressive function of Tr cells. Our data indicate that although 4-1BB is expressed on Tr cells, its contribution to their proliferation is minimal. We also showed that signaling through the 4-1BB receptor inhibited the suppressive function of Tr cells in vitro and in vivo. It is interesting that anti-4-1BB-mediated but not anti-GITR-directed inhibition was more potent when Tr cells were preactivated. Collectively, these data indicate that 4-1BB signaling is critical in Tr cell immunity.
引用
收藏
页码:785 / 791
页数:7
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