| Autor: |
Gray JI; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA., Caron DP; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA., Wells SB; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032 USA., Guyer R; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA., Szabo P; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA., Rainbow D; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Ergen C; Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Rybkina K; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA., Bradley MC; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032 USA., Matsumoto R; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA.; Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032 USA., Pethe K; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032 USA., Kubota M; Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032 USA., Teichmann S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK., Jones J; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Yosef N; Department of Electrical Engineering and Computer Science and Center for Computational Biology, University of California, Berkeley, Berkeley, CA 94720, USA.; Department of Systems Immunology, Weizmann Institute, Rehovot, Israel., Atkinson M; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA., Brusko M; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA., Brusko TM; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611, USA., Connors TJ; Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032 USA., Sims PA; Department of Systems Biology, Columbia University Irving Medical Center, New York, NY 10032 USA.; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA., Farber DL; Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032 USA.; Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032 USA. |
| 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. |
