T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.
T cells that cannot respond to TGF-beta escape control by CD4(+)CD25(+) regulatory T cells.
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DOI：
10.1084/jem.20040685
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发表时间：
2005-03-07
影响因子：
15.3
通讯作者：
Powrie, F
中科院分区：
文献类型：
--
作者：
Fahlén, L;Read, S;Gorelik, L;Hurst, SD;Coffman, RL;Flavell, RA;Powrie, F
CD4 + CD25 +调节性T细胞（Tregs）在免疫应答的控制中起关键作用。转化生长因子 - β（TGF - β）已被证明是Tregs细胞活性所必需的；然而，其在抑制机制中究竟如何参与尚不十分清楚。利用结肠炎的T细胞转移模型，我们在此表明，表达显性负性TGF - β Ⅱ型受体（dnTβRII）因而对TGF - β无反应的CD4 + CD45RB高T细胞在体内逃避了Tregs细胞的控制。来自dnTβRII小鼠胸腺的CD4 + CD25 + Tregs细胞保留抑制结肠炎的能力，这表明T细胞对TGF - β的反应性对于胸腺来源的Tregs细胞的发育或外周功能不是必需的。相反，外周dnTβRII CD4 + CD25 +群体中的Tregs细胞活性被无法被抑制的致结肠炎效应细胞的存在所掩盖。最后，我们表明在缺乏TGF - β1的情况下CD4 + CD25 + Tregs细胞正常发育，并保留在体内抑制结肠炎的能力。重要的是，抗 - TGF - β单克隆抗体可消除TGF - β1 - / - Tregs细胞的功能，这表明功能性TGF - β可由非Tregs细胞来源提供。
CD4+CD25+ regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-β (TGF-β) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4+CD45RBhigh T cells that express a dominant negative TGF-β receptor type II (dnTβRII) and therefore cannot respond to TGF-β, escape control by T reg cells in vivo. CD4+CD25+ T reg cells from the thymus of dnTβRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-β is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTβRII CD4+CD25+ population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4+CD25+ T reg cells develop normally in the absence of TGF-β1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-β1−/− T reg cells was abrogated by anti–TGF-β monoclonal antibody, indicating that functional TGF-β can be provided by a non–T reg cell source.
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DOI：
10.1084/jem.182.5.1357
发表时间：
1995-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Openshaw P;Murphy EE;Hosken NA;Maino V;Davis K;Murphy K;O'Garra A
通讯作者：
O'Garra A
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
白介素10在抑制肠炎的调节T细胞功能中的重要作用。
影响因子：
15.3
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
通讯作者：
Powrie, F
影响因子：
4.4
作者：
Cobbold, SP;Castejon, R;Waldmann, H
通讯作者：
Waldmann, H
影响因子：
4.4
作者：
Asseman, C;Read, S;Powrie, F
通讯作者：
Powrie, F