Retrograde migration supplies resident memory t cells to lung-draining ln after influenza infection

J. Michael Stolley, Timothy S. Johnston, Andrew G. Soerens, Lalit K. Beura, Pamela C. Rosato, Vineet Joag, Sathi P. Wijeyesinghe, Ryan A. Langlois, Kevin C. Osum, Jason S. Mitchell, David Masopust

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate that contraction of lung CD8+ T cell responses after influenza infection is contemporized with egress of CD69+/CD103+ CD8+ T cells to the draining mediastinal LN via the lymphatic vessels, which we term retrograde migration. Cells within the draining LN retained canonical markers of lung TRM, including CD103 and CD69, lacked Ly6C expression (also a feature of lung TRM), maintained granzyme B expression, and did not equilibrate among immunized parabiotic mice. Investigations of bystander infection or removal of the TCR from established memory cells revealed that the induction of the TRM phenotype was dependent on antigen recognition; however, maintenance was independent. Thus, local lung infection induces CD8+ T cells with a TRM phenotype that nevertheless undergo retrograde migration, yet remain durably committed to the residency program within the draining LN, where they provide longer-lived regional memory while chronicling previous upstream antigen experiences.

Original languageEnglish (US)
Article numbere20192197
JournalJournal of Experimental Medicine
Volume217
Issue number8
DOIs
StatePublished - Aug 3 2020

Bibliographical note

Funding Information:
This work was funded by the Howard Hughes Medical Institute Faculty Scholars program, the National Institutes of Health (R01AI084913 to D. Masopust and T90 DE 022732 to J.M. Stolley), and Sinai-Emory Multi-institutional Collaborative Influenza Vaccine Innovation Centers (75N93019C00051 to D. Masopust).

Publisher Copyright:
© 2020 Stolley et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

PubMed: MeSH publication types

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

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