Depleting CD103+ resident memory T cells in vivo reveals immunostimulatory functions in oral mucosa

J. Michael Stolley, Milcah C. Scott, Vineet Joag, Alexander J. Dale, Timothy S. Johnston, Flavia Saavedra, Noah V. Gavil, Sahar Lotfi-Emran, Andrew G. Soerens, Eyob Weyu, Mark J. Pierson, Mark C. Herzberg, Nu Zhang, Vaiva Vezys, David Masopust

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


The oral mucosa is a frontline for microbial exposure and juxtaposes several unique tissues and mechanical structures. Based on parabiotic surgery of mice receiving systemic viral infections or co-housing with microbially diverse pet shop mice, we report that the oral mucosa harbors CD8+ CD103+ resident memory T cells (TRM), which locally survey tissues without recirculating. Oral antigen re-encounter during the effector phase of immune responses potentiated TRM establishment within tongue, gums, palate, and cheek. Upon reactivation, oral TRM triggered changes in somatosensory and innate immune gene expression. We developed in vivo methods for depleting CD103+ TRM while sparing CD103neg TRM and recirculating cells. This revealed that CD103+ TRM were responsible for inducing local gene expression changes. Oral TRM putatively protected against local viral infection. This study provides methods for generating, assessing, and in vivo depleting oral TRM, documents their distribution throughout the oral mucosa, and provides evidence that TRM confer protection and trigger responses in oral physiology and innate immunity.

Original languageEnglish (US)
Article numbere20221853
JournalJournal of Experimental Medicine
Issue number7
StatePublished - Jul 3 2023

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants 5R01AI146032-03, 5R01AI084913-13, and 5R01AI150600-02 (D. Masopust), K99DE031014 and T90 DE 022732 (J.M. Stolley), and the Oral Mucosal Immunity Consortium Windsweep Farm pilot grant (J.M. Stolley and D. Masopust).

Publisher Copyright:
© 2023 Stolley et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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