CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin.
CCR8 Expression Defines Tissue-Resident Memory T Cells in Human Skin.
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DOI：
10.4049/jimmunol.1701377
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发表时间：
2018-03-01
期刊：
影响因子：
--
通讯作者：
Moser B
中科院分区：
文献类型：
--
作者：
McCully ML;Ladell K;Andrews R;Jones RE;Miners KL;Roger L;Baird DM;Cameron MJ;Jessop ZM;Whitaker IS;Davies EL;Price DA;Moser B
人类皮肤有两个大小相等的主要 T 细胞区室，通过趋化因子受体 CCR8 的表达来区分。体外研究表明，CCR8 表达受到 TCR 参与和皮肤组织微环境的调节。为了扩展这些观察结果，我们在体内检查了 CCR8+ 和 CCR8− 皮肤 T 细胞之间的关系。表型、功能和转录组分析显示，CCR8+皮肤T细胞具有常驻记忆T细胞的所有特征，包括响应IL-7和IL-15的稳态增殖、组织定位（CD103）和保留（CD69）标记的表面表达、低水平的抑制性受体（程序性细胞死亡蛋白1、Tim-3、LAG-3）以及缺乏衰老标记 （CD57，杀伤细胞凝集素样受体亚家族 G 成员 1）。相比之下，CCR8− 皮肤 T 细胞是异质的，包含数量不等的耗尽（程序性细胞死亡蛋白 1+）、衰老（CD57+、杀伤细胞凝集素样受体亚家族 G 成员 1+）和效应（T-bethi、Eomeshi）T 细胞。重要的是，对表达的 TCR β 链 (TRB) 基因重排的常规和高通量测序表明，这些 CCR8 定义的群体在克隆型上是不同的，这表明响应单独的抗原挑战和/或刺激条件的独特的个体发育。此外，CCR8+和CCR8−皮肤T细胞在体外表型稳定，并表现出相似的端粒侵蚀水平，进一步支持了非线性分化途径的可能性。基于这些结果，我们提出，人类皮肤中的长寿记忆 T 细胞可以通过 CCR8 的表达来定义。
Human skin harbors two major T cell compartments of equal size that are distinguished by expression of the chemokine receptor CCR8. In vitro studies have demonstrated that CCR8 expression is regulated by TCR engagement and the skin tissue microenvironment. To extend these observations, we examined the relationship between CCR8+ and CCR8− skin T cells in vivo. Phenotypic, functional, and transcriptomic analyses revealed that CCR8+ skin T cells bear all the hallmarks of resident memory T cells, including homeostatic proliferation in response to IL-7 and IL-15, surface expression of tissue localization (CD103) and retention (CD69) markers, low levels of inhibitory receptors (programmed cell death protein 1, Tim-3, LAG-3), and a lack of senescence markers (CD57, killer cell lectin-like receptor subfamily G member 1). In contrast, CCR8− skin T cells are heterogeneous and comprise variable numbers of exhausted (programmed cell death protein 1+), senescent (CD57+, killer cell lectin-like receptor subfamily G member 1+), and effector (T-bethi, Eomeshi) T cells. Importantly, conventional and high-throughput sequencing of expressed TCR β-chain (TRB) gene rearrangements showed that these CCR8-defined populations are clonotypically distinct, suggesting unique ontogenies in response to separate antigenic challenges and/or stimulatory conditions. Moreover, CCR8+ and CCR8− skin T cells were phenotypically stable in vitro and displayed similar levels of telomere erosion, further supporting the likelihood of a nonlinear differentiation pathway. On the basis of these results, we propose that long-lived memory T cells in human skin can be defined by the expression of CCR8.
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影响因子：
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