@article{0bf99bf051ca47e695724383ce8f33d0,
title = "Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the life span",
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 na{\"i}ve 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.",
author = "I. Gray and Caron, {Daniel P.} and Wells, {Steven B.} and Rebecca Guyer and Peter Szabo and Daniel Rainbow and Can Ergen and Ksenia Rybkina and Bradley, {Marissa C.} and Rei Matsumoto and Kalpana Pethe and Masaru Kubota and Sarah Teichmann and Joanne Jones and Nir Yosef and Mark Atkinson and Maigan Brusko and Brusko, {Todd M.} and Connors, {Thomas J.} and Sims, {Peter A.} and Farber, {Donna L.}",
note = "We extend our gratitude to the families whose gift of organ donation through LiveOnNY made this work possible. We acknowledge the dedication and support of M. Yang and R. O{\textquoteright}Flynn from the network for Pancreatic Organ Donors with Diabetes (nPOD), the transplant coordinators and staff of LiveOnNY, and C. Aguilar-Breton and R. Korenberg for the blood sample coordination and collection. We are also grateful to the donors and their families who contributed tissues through the Cambridge Biorepository for Translational Medicine. We thank J. de Barros Martins for helpful comments on this study. Funding: This work was supported by the US National Institutes of Health (NIH) [grants AI106697, AI100119, and AI168634 (to D.L.F.)], grants from the Helmsley Charitable Trust (to D.L.F. and T.B.), and Chan-Zuckerberg Initiative Seed Networks for the Human Cell Atlas [grant CZF2019-002452 (to N.Y., D.L.F., P.A.S., J.J., and S.T)]. J. J. was also supported by NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). T.J.C. was supported by AI141646, and D.P.C. was supported by T32AI106711. Research reported here was performed in the Columbia Flow Cytometry Core (supported by awards S10RR027050 and S10OD020056), the Sulzberger Columbia Genome Center, and the Columbia Single Cell Analysis Core (supported by grant P30-CA013696). Additional support was provided by Columbia University{\textquoteright}s CTSA grant no. UL1TR001873 from NCATS/NIH. The content is solely the responsibility of the authors and does not necessarily represent official views of the NIH.",
year = "2024",
month = jun,
doi = "10.1126/sciimmunol.adn3954",
language = "الإنجليزيّة",
volume = "9",
journal = "Science Immunology",
issn = "2470-9468",
publisher = "American Association for the Advancement of Science",
number = "96",
}