Generation and persistence of human tissue-resident memory T cells in lung transplantation.

Autor: Snyder ME; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA., Finlayson MO; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA., Connors TJ; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA., Dogra P; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA., Senda T; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA., Bush E; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA., Carpenter D; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA., Marboe C; Department of Pathology, Columbia University Medical Center, New York, NY 10032, USA., Benvenuto L; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA., Shah L; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA., Robbins H; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA., Hook JL; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA., Sykes M; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA., D'Ovidio F; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA., Bacchetta M; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA., Sonett JR; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA., Lederer DJ; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY 10032, USA., Arcasoy S; Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.; Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA., Sims PA; Department of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA., Farber DL; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. df2396@cumc.columbia.edu.; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.; Department of Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2019 Mar 08; Vol. 4 (33).
DOI: 10.1126/sciimmunol.aav5581
Abstrakt: Tissue-resident memory T cells (T RM ) maintain immunity in diverse sites as determined in mouse models, whereas their establishment and role in human tissues have been difficult to assess. Here, we investigated human lung T RM generation, maintenance, and function in airway samples obtained longitudinally from human leukocyte antigen (HLA)-disparate lung transplant recipients, where donor and recipient T cells could be localized and tracked over time. Donor T cells persist specifically in the lungs (and not blood) of transplant recipients and express high levels of T RM signature markers including CD69, CD103, and CD49a, whereas lung-infiltrating recipient T cells gradually acquire T RM phenotypes over months in vivo. Single-cell transcriptome profiling of airway T cells reveals that donor T cells comprise two T RM -like subsets with varying levels of expression of T RM -associated genes, whereas recipient T cells comprised non-T RM and similar T RM -like subpopulations, suggesting de novo T RM generation. Transplant recipients exhibiting higher frequencies of persisting donor T RM experienced fewer adverse clinical events such as primary graft dysfunction and acute cellular rejection compared with recipients with low donor T RM persistence, suggesting that monitoring T RM dynamics could be clinically informative. Together, our results provide spatial and temporal insights into how human T RM develop, function, persist, and affect tissue integrity within the complexities of lung transplantation.
(Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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