TCR usage, gene expression and function of two distinct FOXP3+Treg subsets within CD4+CD25hi T cells identified by expression of CD39 and CD45RO
TCR usage, gene expression and function of two distinct FOXP3+Treg subsets within CD4+CD25hi T cells identified by expression of CD39 and CD45RO
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通过 CD39 和 CD45RO 表达鉴定的 CD4 CD25hi T 细胞内两个不同 FOXP3 Treg 亚群的 TCR 使用、基因表达和功能
DOI：
10.1038/icb.2015.90
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发表时间：
2016-03-01
影响因子：
4
通讯作者：
Xu, Huji
中科院分区：
文献类型：
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作者：
Ye, Lingying;Goodall, Jane C.;Xu, Huji
FOXP3+调节性T （Treg）细胞对于免疫稳态是必不可少的，但由于Treg内部的异质性、使用表面标记物表达（如CD25）纯化Treg的困难以及激活的效应细胞瞬间表达FOXP3，使其在人体中的研究变得复杂。在这里，我们报告了CD39和CD45RO的表达区分了人类CD4+CD25hi T细胞中的三个亚群。初始表型和功能分析表明，CD4+CD25hiCD39+CD45RO+细胞具有与效应T细胞一致的特性，CD4+CD25hiCD39 - CD45RO -细胞具有naïve Treg功能，CD4+CD25hiCD39 - CD45RO+细胞主要是非Treg细胞，具有效应T细胞功能。基因表达研究和TCR分析证实了这两个新发现的Treg亚群的差异。为了应用这种方法，我们研究了强直性脊柱炎中这两个新发现的Treg亚群，并显示了效应和naïve Treg的损伤。这项工作强调了鉴别Treg亚群的重要性，以便对健康个体和炎症性疾病患者的免疫调节能力进行适当的比较。
FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub‐populations within human CD4+CD25hi T cells. Initial phenotypic and functional analysis demonstrated that CD4+CD25hiCD39+CD45RO+ cells had properties consistent with effector Treg, CD4+CD25hiCD39−CD45RO− cells were naïve Treg and CD4+CD25hiCD39−CD45RO+ cells were predominantly non‐Treg with effector T‐cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.