抑制器
转化生长因子
白细胞介素2受体
细胞生物学
癌症研究
转化生长因子β
免疫疗法
体外
下调和上调
化学
生物
T细胞
免疫学
免疫系统
基因
生物化学
作者
Guohua Wang,Mithun Khattar,Zhiyong Guo,Yoshihiro Miyahara,Sean P. Linkes,Zhen Sun,Xiaoshun He,Stanislaw M. Stepkowski,Wenhao Chen
标识
DOI:10.1016/j.imlet.2010.06.001
摘要
The benefits of immunotherapy by regulatory T (Treg) cells are unpredictable partially due to the uncertainty of their suppressive mechanism. In fact, various suppressive mechanisms have been proposed but each remains controversial. To better understand Treg-mediated suppression, we have investigated factors which may influence the suppressive effects. In an in vitro suppression assay, over-expression of anti-apoptotic Bcl2 enhancing survival of conventional T responder cells (Tconvs) did not subvert Treg-mediated suppression. In contrast, enhancing activation of Tconvs by increasing the potency of calcium signals completely abrogated Treg-mediated suppression. While Tregs were incapable of suppressing already activated Tconvs, they prevented expression of activation markers on naïve Tconvs during activation, thereby indicating that Tregs mediate suppression through controlling early activation stage. Interestingly, IL-2 deprivation or TGF-beta, two suppressive mechanisms, did not effectively inhibit Tconv activation and proliferation when applied alone. In contrast, IL-2 deprivation combined with TGF-beta suppressed Tconv activation as potently as Tregs. More importantly, in the transwell system, that separates Tregs from Tconvs, TGF-beta contributed to Treg suppression under IL-2 depriving condition. In conclusion, these two suppressive mechanisms acting in concert may be necessary to effectively restrain the early activation of Tconvs.
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