Tissue‐resident regulatory T cells accumulate at human barrier lymphoid organs

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/imcb.12481
Journal or Publication Title: Immunology & Cell Biology
Volume: 99
Number: 8
Page Range: pp. 894-906
Date: September 2021
Divisions: Tuberculosis
Human Viral and Cancer Immunology
Depositing User: General Admin
Identification Number: 10.1111/imcb.12481
ISSN: 0818-9641
Date Deposited: 10 Oct 2021 10:45
Abstract:

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.

Keywords: T follicular helper cells; T follicular regulatory; Tregs; tissue-resident memory T cells.

© 2021 Australian and New Zealand Society for Immunology, Inc.

Creators:
Creators
Email
Hewavisenti, Rehana V
UNSPECIFIED
Ferguson, Angela L
UNSPECIFIED
Gasparini, Georgia
UNSPECIFIED
Ohashi, Tomoki
UNSPECIFIED
Braun, Asolina
UNSPECIFIED
Watkins, Thomas S
UNSPECIFIED
Miles, John J
UNSPECIFIED
Elliott, Michael
UNSPECIFIED
Sierro, Frederic
UNSPECIFIED
Feng, Carl G
UNSPECIFIED
Britton, Warwick J
UNSPECIFIED
Gebhardt, Thomas
UNSPECIFIED
Tangye, Stuart
UNSPECIFIED
Palendira, Umaimainthan
UNSPECIFIED
Last Modified: 10 Oct 2021 10:45
URI: https://eprints.centenary.org.au/id/eprint/1088

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