Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-β-dependent mechanism
Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-β-dependent mechanism
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DOI：
10.1073/pnas.0708350105
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发表时间：
2008-02-19
影响因子：
11.1
通讯作者：
Valitutti, Salvatore
中科院分区：
文献类型：
--
作者：
Esquerre, Michael;Tauzin, Baptiste;Valitutti, Salvatore
调节性T细胞（Treg）抑制适应性免疫应答效应期的分子机制仍然难以捉摸。在目前的工作中，我们研究了Treg可能干扰T辅助细胞（T-H）的基本生物学功能的可能性：专门帮助传递的分泌机制的极化。为了解决这个问题，我们通过共聚焦显微镜观察了T-H和Treg细胞与单个抗原呈递细胞（APC）同时相互作用的不同激活参数。我们的研究结果表明，虽然生产TCR参与T-H/APC结合物的存在下，相邻的Treg的影响，T-H分泌机制向APC的重定向强烈抑制。阻断TGF-β完全逆转了Treg诱导的T-H极化抑制。我们的研究结果确定了一个以前未描述的机制，Treg抑制效应T细胞。由相邻Treg产生的TGF-β干扰T-H分泌机制向APC的极化，从而影响T-H介导的免疫应答扩增的关键步骤。
The molecular mechanisms used by regulatory T cells (Treg) to inhibit the effector phase of adaptive immune responses are still elusive. In the present work, we investigated the possibility that Treg may interfere with a basic biological function of T helper cells (T-H): polarization of secretory machinery for dedicated help delivery. To address this question, we visualized by confocal microscopy different parameters of activation in T-H and Treg cells interacting simultaneously with individual antigen-presenting cells (APC). Our results show that, although productive TCR engagement in T-H/APC conjugates was unaffected by the presence of adjacent Treg, the reorientation of T-H secretory machinery toward APC was strongly inhibited. Blocking TGF-beta completely reverted Treg induced inhibition of T-H polarization. Our results identify a previously undescribed mechanism by which Treg inhibit effector T cells. TGF-beta produced by adjacent Treg interferes with polarization of T-H secretory machinery toward APC, thus affecting a crucial step of T-H-mediated amplification of the immune response.