Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells
Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells
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DOI：
10.1038/ncomms3209
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发表时间：
2013-07-01
影响因子：
16.6
通讯作者：
Lucas, Bruno
中科院分区：
文献类型：
--
作者：
Martin, Bruno;Auffray, Cedric;Lucas, Bruno
在活化后，初始CD4 T细胞分化成以不同细胞因子产生和功能为特征的多种T辅助细胞亚群。目前，谱系定型被认为主要取决于幼稚CD4 T细胞所暴露的环境背景。在这里，我们挑战这个模型的基础上假设的同质性的幼稚CD4 T细胞室。我们发现，外周幼稚CD4 T细胞可以分为两个亚群根据Ly-6C的表达。此外，两个新定义的亚群（Ly-6C（-）和Ly-6C（+）初始CD4 T细胞）在其固有的定型为诱导的调节性T细胞谱系的能力上是不相等的。最后，表型分析，成像和过继转移实验表明，Ly-6C的表达是由自我识别调制，允许幼稚的CD4 T细胞区室的二分成两个细胞亚群具有不同的自身反应性。总之，我们的研究结果表明，具有最高亲合力的初始CD4 T细胞倾向于分化为调节性T细胞。
Upon activation, naive CD4 T cells differentiate into a variety of T-helper-cell subsets characterized by different cytokine production and functions. Currently, lineage commitment is considered to depend mostly on the environmental context to which naive CD4 T cells are exposed. Here we challenge this model based on the supposed homogeneity of the naive CD4 T-cell compartment. We show that peripheral naive CD4 T cells can be subdivided into two subsets according to Ly-6C expression. Furthermore, the two newly defined subsets (Ly-6C(-) and Ly-6C(+) naive CD4 T cells) are not equal in their intrinsic ability to commit into the induced regulatory T-cell lineage. Finally, phenotypic analysis, imaging and adoptive transfer experiments reveal that Ly-6C expression is modulated by self-recognition, allowing the dichotomization of the naive CD4 T-cell compartment into two cell subsets with distinct self-reactivity. Altogether, our results show that naive CD4 T cells with the highest avidity for self are prone to differentiate into regulatory T cells.