Cervicovaginal tissue residence confers a distinct differentiation program upon memory CD8 T cells

Veronica A. Davé, E. Fabian Cardozo-Ojeda, Florian Mair, Jami Erickson, Amanda S. Woodward-Davis, Amanda Koehne, Andrew Soerens, Julie Czartoski, Candice Teague, Nicole Potchen, Susanne Oberle, Dietmar Zehn, Joshua T. Schiffer, Jennifer M. Lund, Martin Prlic

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue-resident memory CD8 T cells (CD8 TRM) are critical for maintaining barrier immunity. CD8 TRM have been mainly studied in the skin, lung and gut, with recent studies suggesting that the signals that control tissue residence and phenotype are highly tissue dependent. We examined the T cell compartment in healthy human cervicovaginal tissue (CVT) and found that most CD8 T cells were granzyme B+ and TCF-1-. To address if this phenotype is driven by CVT tissue residence, we used a mouse model to control for environmental factors. Using localized and systemic infection models, we found that CD8 TRM in the mouse CVT gradually acquired a granzyme B+, TCF-1-phenotype as seen in human CVT. In contrast to CD8 TRM in the gut, these CD8 TRM were not stably maintained regardless of the initial infection route, which led to reductions in local immunity. Our data show that residence in the CVT is sufficient to progressively shape the size and function of its CD8 TRM compartment.

Original languageEnglish (US)
Pages (from-to)2937-2948
Number of pages12
JournalJournal of Immunology
Volume206
Issue number12
Early online dateMay 4 2021
DOIs
StatePublished - Jun 15 2021
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) Grants R01AI123323 (M.P.), R01 AI121129 (J.T.S., J.M.L., and M.P.), R01 AI131914 (J.M.L.), R01 AI141435 (J.M.L.), and T32 AI07140, the Doug and Maggie Walker Fellowship (A.S.W.-D.), NIH Grant T32 AI007509, and Division of Intramural Research, National Institute of Allergy and Infectious Diseases Grant F31 AI140514 (V.A.D.). F.M. is an International Society for Advancement of Cytometry scholar.

Funding Information:
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) Grants R01AI123323 (M.P.), R01 AI121129 (J.T.S., J.M.L., and M.P.), R01 AI131914 (J.M.L.), R01 AI141435 (J.M.L.), and T32 AI07140, the Doug and

Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.

PubMed: MeSH publication types

  • Journal Article

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