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

Autor: Gray, Joshua I., Caron, Daniel P., Wells, Steven B., Guyer, Rebecca, Szabo, Peter, Rainbow, Daniel, Ergen, Can, Rybkina, Ksenia, Bradley, Marissa C., Matsumoto, Rei, Pethe, Kalpana, Kubota, Masaru, Teichmann, Sarah, Jones, Joanne, Yosef, Nir, Atkinson, Mark, Brusko, Maigan, Brusko, Todd M., Connors, Thomas J., Sims, Peter A.
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Zdroj: Science Immunology; 2024, Vol. 9 Issue 96, p1-15, 15p
Abstrakt: 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. Editor's summary: Our understanding of the functional role of human γδ T cells in tissues is very limited and has been primarily informed by peripheral blood studies. Gray et al. used a multiomics strategy to characterize human γδ T cells in the blood and various mucosal and lymphoid tissues from 176 donors whose ages ranged from just a few days to over 80 years. In contrast to the highly differentiated and cytotoxic γδ T cell populations found in adults, γδ T cells during infancy and childhood are clonally diverse, are tissue specific, and exhibit features of adaptive lymphocytes. —Seth Thomas Scanlon [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index