During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity. However, their functional role in humans has largely been defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood and mucosal and lymphoid tissues from 176 donors across the life span, revealing distinct profiles in children compared with adults. In early life, clonally diverse Vδ1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, whereas cytolytic Vδ2 subsets populate blood, spleen, and lungs. With age, Vδ1 and Vδ2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, Vδ2 cells predominate in blood, whereas Vδ1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.

中文翻译：

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不同组织中的人类 γδ T 细胞在整个生命周期中表现出位点特异性成熟动态


在个体发育过程中，γδ T 细胞从胸腺中出现并直接播种到外周组织中以实现原位免疫。然而，它们在人类中的功能作用很大程度上是通过血液来定义的。在这里，我们分析了 176 名捐献者整个生命周期中血液、粘膜和淋巴组织中人类 γδ T 细胞的表型、转录组、功能和全部功能，揭示了儿童与成人的不同特征。在生命早期，克隆多样化的 Vδ1 亚群在血液和组织中占主导地位，包括幼稚和分化的效应器和组织修复功能，而细胞溶解性 Vδ2 亚群则分布在血液、脾脏和肺中。随着年龄的增长，Vδ1 和 Vδ2 亚群表现出克隆扩张和细胞溶解特征升高，并在各个位点传播。在成人中，Vδ2 细胞在血液中占主导地位，而 Vδ1 细胞在组织中富集并表达驻留特征。因此，童年时期的抗原暴露驱动了 γδ T 细胞的功能进化和组织区室化，从而导致免疫中年龄依赖性的作用。