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

被引：9

作者：

Gray, Joshua I. ^{[1
]}

Caron, Daniel P. ^{[1
]}

Wells, Steven B. ^{[2
]}

Guyer, Rebecca ^{[1
]}

Szabo, Peter ^{[1
]}

Rainbow, Daniel ^{[3
]}

Ergen, Can ^{[4
,5
]}

Rybkina, Ksenia ^{[1
]}

Bradley, Marissa C. ^{[6
]}

Matsumoto, Rei ^{[1
,7
]}

Pethe, Kalpana ^{[6
]}

Kubota, Masaru ^{[7
]}

Teichmann, Sarah ^{[8
]}

Jones, Joanne ^{[3
]}

Yosef, Nir ^{[4
,5
,9
]}

Atkinson, Mark ^{[10
]}

Brusko, Maigan ^{[10
]}

Brusko, Todd M. ^{[10
]}

Connors, Thomas J. ^{[6
]}

Sims, Peter A. ^{[2
,11
]}

Farber, Donna L. ^{[1
,7
]}

机构：

[1] Columbia Univ, Irving Med Ctr, Dept Microbiol & Immunol, New York, NY 10032 USA

[2] Columbia Univ, Irving Med Ctr, Dept Syst Biol, New York, NY 10032 USA

[3] Univ Cambridge, Dept Clin Neurosci, Cambridge, England

[4] Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA

[5] Univ Calif Berkeley, Ctr Computat Biol, Berkeley, CA 94720 USA

[6] Columbia Univ, Vagelos Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA

[7] Columbia Univ, Dept Surg, Irving Med Ctr, New York, NY 10032 USA

[8] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England

[9] Weizmann Inst Sci, Dept Syst Immunol, Rehovot, Israel

[10] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA

[11] Columbia Univ, Irving Med Ctr, Dept Biochem & Mol Biophys, New York, NY 10032 USA

来源：

SCIENCE IMMUNOLOGY | 2024年 / 9卷 / 96期

基金：

美国国家卫生研究院;

关键词：

IMMUNE-RESPONSE; TERMINAL DIFFERENTIATION; HUMAN NK; MEMORY; TRAFFICKING; INFLAMMATION; RECEPTORS; EFFECTOR; SUBSET; SKIN;

D O I：

10.1126/sciimmunol.adn3954

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

During ontogeny, gamma delta 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 gamma delta 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 V delta 1 subsets predominate across blood and tissues, comprising na & iuml;ve and differentiated effector and tissue repair functions, whereas cytolytic V delta 2 subsets populate blood, spleen, and lungs. With age, V delta 1 and V delta 2 subsets exhibit clonal expansions and elevated cytolytic signatures, which are disseminated across sites. In adults, V delta 2 cells predominate in blood, whereas V delta 1 cells are enriched across tissues and express residency profiles. Thus, antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of gamma delta T cells, leading to age-dependent roles in immunity.

引用

页数：15