Developmental Progression and Interrelationship of Central and Effector Regulatory T Cell Subsets.
Developmental Progression and Interrelationship of Central and Effector Regulatory T Cell Subsets.
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DOI：
10.4049/jimmunol.1500595
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发表时间：
2016-05-01
期刊：
影响因子：
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通讯作者：
Malek TR
中科院分区：
文献类型：
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作者：
Toomer KH;Yuan X;Yang J;Dee MJ;Yu A;Malek TR
自身耐受需要静息的中枢T细胞（cT细胞）和激活的效应T细胞（eT细胞），但cT细胞和eT细胞的表型不同的子集内和之间的异质性和关系知之甚少。通过广泛的免疫分析和TCRβ V区的深度测序，鉴定了基于Ly-6C表达的两个cT细胞亚群和基于CD 62 L、CD 69和CD 103独特表达的三个eT细胞亚群。与Ly-6C − cTCRs相比，Ly-6C+ cTCRs表现出较低的基础活化，平均表达较低亲和力的TCR，并且发展成eTCRs的效率较低。Ly-6C+ cTcR的优势TCR Vβs为eTcR所共有，频率较低。还鉴定了单个TCR克隆型，其在很大程度上仅限于Ly-6C+ cTf 3，即使在促进eTf 3发展的条件下。总的来说，这些发现表明，一些Ly-6C+ cTdR可能作为淋巴特异性亚群持续存在，发展为高度活化的eTdR的可能性极小，而其他cTdR容易发展为eTdR。相比之下，CD 62 LloeTcR亚群显示出更高的克隆扩增，并且基于其TCRβ库比cTreg亚群更高度地相互关联，但表现出不同的免疫特征。CD 62 Llo CD 69 − CD 103 − eTreg亚群显示出cTlag和更活化的eTreg亚群之间的过渡中间体的性质。因此，eT细胞亚群似乎表现出很大的灵活性，可能是响应于环境线索，以采用预期优化自身反应性T细胞抑制的定义的免疫谱。
Resting central Tregs (cTregs) and activated effector Tregs (eTregs) are required for self-tolerance, but the heterogeneity and relationships within and between phenotypically distinct subsets of cTregs and eTregs are poorly understood. By extensive immune profiling and deep sequencing of TCRβ V-regions, two subsets of cTregs, based on expression of Ly-6C, and three subsets of eTregs, based on distinctive expression of CD62L, CD69, and CD103, were identified. Ly-6C+ cTregs exhibited lower basal activation, expressed on average lower affinity TCRs, and less efficiently developed into eTregs when compared to Ly-6C− cTregs. The dominant TCR Vβs of Ly-6C+ cTregs were shared by eTregs at a low frequency. A single TCR clonotype was also identified that was largely restricted to Ly-6C+ cTregs, even under conditions that promoted the development of eTregs. Collectively, these findings indicate that some Ly-6C+ cTregs may persist as a lymphoid-specific subset, with minimal potential to develop into highly activated eTregs, while other cTregs readily develop into eTregs. In contrast, subsets of CD62Llo eTregs showed higher clonal expansion and were more highly inter-related than cTreg subsets based on their TCRβ repertoires, but exhibited varied immune profiles. The CD62Llo CD69− CD103− eTreg subset displayed properties of a transitional intermediate between cTregs and more activated eTreg subsets. Thus, eTregs subsets appear to exhibit substantial flexibility, likely in response to environmental cues, to adopt defined immune profiles that are expected to optimize suppression of autoreactive T cells.