Tissue-resident regulatory T cells accumulate at human barrier lymphoid organs.

Autor: Hewavisenti RV; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Centenary Institute, The University of Sydney, Sydney, NSW, Australia., Ferguson AL; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Centenary Institute, The University of Sydney, Sydney, NSW, Australia.; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia., Gasparini G; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Ohashi T; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia., Braun A; Department of Immunology and Microbiology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia., Watkins TS; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Miles JJ; Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, QLD, Australia., Elliott M; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.; Chris O'Brien Lifehouse Cancer Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia., Sierro F; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Australian Nuclear Science and Technology Organisation, Sydney, NSW, Australia., Feng CG; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Centenary Institute, The University of Sydney, Sydney, NSW, Australia.; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia., Britton WJ; Centenary Institute, The University of Sydney, Sydney, NSW, Australia.; Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia., Gebhardt T; Department of Immunology and Microbiology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia., Tangye S; Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.; St Vincent's Clinical School, UNSW Sydney, Darlinghurst, NSW, Australia., Palendira U; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.; Centenary Institute, The University of Sydney, Sydney, NSW, Australia.; Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia.
Jazyk: angličtina
Zdroj: Immunology and cell biology [Immunol Cell Biol] 2021 Sep; Vol. 99 (8), pp. 894-906. Date of Electronic Publication: 2021 Jul 27.
DOI: 10.1111/imcb.12481
Abstrakt: Regulatory T cells (Tregs) play a critical role in immune regulation and peripheral tolerance. While different types of Tregs have been identified in both mice and humans, much of our understanding about how these cells maintain immune homeostasis is derived from animal models. In this study, we examined two distinct human lymphoid organs to understand how repeated exposure to infections at the mucosal surface influences the phenotype and tissue localization of Tregs. We show that while Tregs in both tonsils and spleen express a tissue-resident phenotype, they accumulate in greater numbers in tonsils. Tonsillar-resident Tregs exhibit a highly suppressive phenotype with significantly increased expression of CD39, ICOS and CTLA-4 compared with their counterparts in circulation or in the spleen. Functionally, resident Tregs are able effectively to suppress T cell proliferation. We further demonstrate that tonsillar-resident Tregs share key features of T follicular helper cells. Spatial analysis reveals that the vast majority of resident Tregs are localized at the border of the T-zone and B cell follicle, as well as within the lymphocyte pockets enriched with resident memory T cells. Together our findings suggest that resident Tregs are strategically co-localized to maintain immune homeostasis at sites of recurrent inflammation.
(© 2021 Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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