CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness.
CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness.
复制标题
DOI：
10.1084/jem.20020590
复制
发表时间：
2002-07-15
期刊：
影响因子：
--
通讯作者：
Shevach EM
中科院分区：
文献类型：
--
作者：
Piccirillo CA;Letterio JJ;Thornton AM;McHugh RS;Mamura M;Mizuhara H;Shevach EM
CD4+CD25+调节性T细胞抑制由CD4+CD25−T细胞诱导的器官特异性自身免疫性疾病，并且是体外T细胞活化的有效抑制因子。它们的抑制机制尚不清楚，但大多数体外研究表明，它是细胞接触依赖和细胞因子独立的。TGF-β1在CD4+CD25+抑制功能中的作用尚不清楚。虽然大多数研究未能在体外逆转抗转化生长因子(TGF)-β1的抑制，但最近的一项研究报道，CD4+CD25+ T细胞表达细胞表面TGF-β1，高浓度的抗TGF-β可完全消除这种抑制，这表明细胞相关的TGF-β1是CD4+CD25+介导的抑制的主要效应者。在这里，我们重新评估了TGF-β1在CD4+CD25+介导的抑制中的作用。单克隆抗体（mAb）或可溶性TGF-βRII-Fc中和TGF-β1均不能逆转静止或活化CD4+CD25+ T细胞介导的体外抑制。来自Smad3−/−或显性阴性TGF-β型RII转基因（DNRIITg）小鼠的应答T细胞，对TGF-β1诱导的生长停滞均无反应，与野生型小鼠的T细胞一样容易受到CD4+CD25+介导的抑制。此外，新生TGF-β1−/−小鼠的CD4+CD25+ T细胞与TGF-β1+/+小鼠的CD4+CD25+ T细胞具有相同的抑制作用。综上所述，这些结果表明CD4+CD25+抑制功能可以独立于TGF-β1发生。
CD4+CD25+ regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4+CD25−T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact–dependent and cytokine independent. The role of TGF-β1 in CD4+CD25+ suppressor function remains unclear. While most studies have failed to reverse suppression with anti–transforming growth factor (TGF)-β1 in vitro, one recent study has reported that CD4+CD25+ T cells express cell surface TGF-β1 and that suppression can be completely abrogated by high concentrations of anti–TGF-β suggesting that cell-associated TGF-β1 was the primary effector of CD4+CD25+-mediated suppression. Here, we have reevaluated the role of TGF-β1 in CD4+CD25+-mediated suppression. Neutralization of TGF-β1 with either monoclonal antibody (mAb) or soluble TGF-βRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4+CD25+ T cells. Responder T cells from Smad3−/− or dominant-negative TGF-β type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-β1–induced growth arrest, were as susceptible to CD4+CD25+-mediated suppression as T cells from wild-type mice. Furthermore, CD4+CD25+ T cells from neonatal TGF-β1−/− mice were as suppressive as CD4+CD25+ from TGF-β1+/+ mice. Collectively, these results demonstrate that CD4+CD25+ suppressor function can occur independently of TGF-β1.
登录
查看更多内容
DOI：
10.1084/jem.193.11.1303
发表时间：
2001-06-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dieckmann D;Plottner H;Berchtold S;Berger T;Schuler G
通讯作者：
Schuler G
人CD25（+）CD4（+）T调节细胞抑制幼稚和记忆T细胞增殖，可以在体外扩展而不会失去功能。
影响因子：
15.3
作者：
Levings, M K;Sangregorio, R;Roncarolo, M G
通讯作者：
Roncarolo, M G
影响因子：
32.4
作者：
Gorelik, L;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
56.9
作者：
KATZ, JD;BENOIST, C;MATHIS, D
通讯作者：
MATHIS, D
DOI：
10.1016/s0167-5699(99)01510-8
发表时间：
1999-10-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Groux, H;Powrie, F
通讯作者：
Powrie, F