Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span

IF 17.6 1区 医学 Q1 IMMUNOLOGY Science Immunology Pub Date : 2024-06-07 DOI:10.1126/sciimmunol.adn3954
Joshua I. Gray, Daniel P. Caron, Steven B. Wells, Rebecca Guyer, Peter Szabo, Daniel Rainbow, Can Ergen, Ksenia Rybkina, Marissa C. Bradley, Rei Matsumoto, Kalpana Pethe, Masaru Kubota, Sarah Teichmann, Joanne Jones, Nir Yosef, Mark Atkinson, Maigan Brusko, Todd M. Brusko, Thomas J. Connors, Peter A. Sims, Donna L. Farber
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Abstract

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.

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不同组织中的人γδ T 细胞在整个生命周期中表现出特定部位的成熟动态。
在本体发育过程中,γδ T 细胞从胸腺中萌发并直接播种到外周组织中,以实现原位免疫。然而,γδT 细胞在人体中的功能作用主要是从血液中确定的。在这里,我们分析了 176 名捐献者的血液、粘膜和淋巴组织中人类γδ T 细胞在整个生命周期中的表型、转录组、功能和细胞群。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,而细胞溶解性 Vδ2 亚群则遍布血液、脾脏和肺部。随着年龄的增长,Vδ1 和 Vδ2 亚群表现出克隆扩张和细胞溶解特征的增强,并在不同部位扩散。在成人中,Vδ2 细胞在血液中占主导地位,而 Vδ1 细胞则富集于各组织中,并表达驻留特征。因此,童年时期的抗原暴露推动了γδT细胞的功能进化和组织分区,导致其在免疫中发挥与年龄相关的作用。
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来源期刊
Science Immunology
Science Immunology Immunology and Microbiology-Immunology
CiteScore
32.90
自引率
2.00%
发文量
183
期刊介绍: Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.
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