Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA.
Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032 USA.
Sci Immunol. 2024 Jun 7;9(96):eadn3954. doi: 10.1126/sciimmunol.adn3954.
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.
在个体发育过程中，γδ T 细胞从胸腺中出现，并直接在原位免疫中播种到外周组织。然而，它们在人类中的功能作用在很大程度上是从血液中定义的。在这里，我们分析了 176 名供体在整个生命周期中的血液、粘膜和淋巴组织中的人类 γδ T 细胞的表型、转录组、功能和 repertoire，揭示了儿童与成人相比的独特特征。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细胞和组织修复功能，而细胞毒性 Vδ2 亚群则存在于血液、脾脏和肺部。随着年龄的增长，Vδ1 和 Vδ2 亚群表现出克隆扩增和升高的细胞毒性特征，这些特征在各个部位传播。在成年人中，Vδ2 细胞在血液中占优势，而 Vδ1 细胞在组织中富集，并表达居留特征。因此，儿童时期的抗原暴露驱动 γδ T 细胞的功能进化和组织区室化，导致其在免疫中具有年龄依赖性作用。
