IL-2-deprivation and TGF-beta are two non-redundant suppressor mechanisms of CD4+CD25+ regulatory T cell which jointly restrain CD4+CD25- cell activation.
IL-2-deprivation and TGF-beta are two non-redundant suppressor mechanisms of CD4+CD25+ regulatory T cell which jointly restrain CD4+CD25- cell activation.
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DOI：
10.1016/j.imlet.2010.06.001
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发表时间：
2010-08-16
影响因子：
4.4
通讯作者：
Chen, Wenhao
中科院分区：
文献类型：
--
作者：
Wang, Guohua;Khattar, Mithun;Guo, Zhiyong;Miyahara, Yoshihiro;Linkes, Sean P.;Sun, Zongquan;He, Xiaoshun;Stepkowski, Stanislaw M.;Chen, Wenhao
调节性 T (Treg) 细胞免疫治疗的益处是不可预测的，部分原因是其抑制机制的不确定性。事实上，已经提出了各种抑制机制，但每种机制仍存在争议。为了更好地了解 Treg 介导的抑制，我们研究了可能影响抑制效果的因素。在体外抑制测定中，抗凋亡 Bcl2 的过度表达可增强传统 T 反应细胞 (Tconv) 的存活，但不会破坏 Treg 介导的抑制。相反，通过增加钙信号的效力来增强 Tconv 的激活完全消除了 Treg 介导的抑制。虽然 Tregs 无法抑制已经激活的 Tconv，但它们在激活过程中阻止了幼稚 Tconv 上激活标记的表达，从而表明 Tregs 通过控制早期激活阶段介导抑制。有趣的是，IL-2 剥夺或 TGF-β 这两种抑制机制单独应用时并不能有效抑制 Tconv 激活和增殖。相比之下，IL-2 剥夺与 TGF-β 结合可像 Tregs 一样有效地抑制 Tconv 激活。更重要的是，在将Treg与Tconv分开的transwell系统中，TGF-β在IL-2剥夺条件下有助于抑制Treg。总之，这两种抑制机制协同作用可能是有效抑制 Tconv 早期激活所必需的。
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-β, two suppressive mechanisms, did not effectively inhibit Tconv activation and proliferation when applied alone. In contrast, IL-2 deprivation combined with TGF-β suppressed Tconv activation as potently as Tregs. More importantly, in the transwell system, that separates Tregs from Tconvs, TGF-β 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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影响因子：
15.3
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
通讯作者：
Powrie, F
DOI：
10.1007/s00005-009-0021-1
发表时间：
2009-05-01
影响因子：
3.2
作者：
Khattar, Mithun;Chen, Wenhao;Stepkowski, Stanislaw M.
通讯作者：
Stepkowski, Stanislaw M.
影响因子：
32.4
作者：
Li, Ming O.;Wan, Yisong Y.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
4.4
作者：
Nakamura, K;Kitani, A;Strober, W
通讯作者：
Strober, W
影响因子：
20.3
作者：
Garin, Marina I.;Chu, Chung-Ching;Lechler, Robert I.
通讯作者：
Lechler, Robert I.