Cutting edge:: The natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression
Cutting edge:: The natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression
复制标题
DOI：
10.4049/jimmunol.172.10.5823
复制
发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Terhorst, C
中科院分区：
文献类型：
--
作者：
Ji, HB;Liao, GX;Terhorst, C
CD 4（+）25（+）调节性T（Treg）细胞通过仅部分理解的机制维持免疫自身耐受。先前的研究表明，糖皮质激素诱导的TNFR相关蛋白（GITR），它优先表达在Treg细胞的表面，可能提供一个信号，废除Treg抑制。在这项研究中，我们表明，可溶形式的小鼠GITR配体（sGITR-L）诱导GITR依赖性NF-κ B活化，并阻断由静息和预活化的多克隆和Ag特异性Treg细胞介导的体外抑制。由于sGITR-L沿着rIL-2诱导CD 4（+）25（+）细胞增殖，因此似乎GITR-L可以打破Treg细胞的无能状态。由于sGITR-L还上调活化的CD 4（+）25（-）T细胞的IL-2分泌，这两种sGITR-L诱导的信号协同作用以干扰CD 4（+）25（+）Treg细胞的抑制活性。
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.