CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses

Lalit K. Beura, Nancy J. Fares-Frederickson, Elizabeth M. Steinert, Milcah C. Scott, Emily A. Thompson, Kathryn A. Fraser, Jason M. Schenkel, Vaiva Vezys, David Masopust

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

This study examines the extent to which memory CD4+ T cells share immunosurveillance strategies with CD8+ resident memory T cells (TRM). After acute viral infection, memory CD4+ T cells predominantly used residence to survey nonlymphoid tissues, albeit not as stringently as observed for CD8+ T cells. In contrast, memory CD4+ T cells were more likely to be resident within lymphoid organs than CD8+ T cells. Migration properties of memory-phenotype CD4+ T cells in non-SPF parabionts were similar, generalizing these results to diverse infections and conditions. CD4+ and CD8+ TRM shared overlapping transcriptional signatures and location-specific features, such as granzyme B expression in the small intestine, revealing tissue-specific and migration property–specific, in addition to lineage-specific, differentiation programs. Functionally, mucosal CD4+ TRM reactivation locally triggered both chemokine expression and broad immune cell activation. Thus, residence provides a dominant mechanism for regionalizing CD4+ T cell immunity, and location enforces shared transcriptional, phenotypic, and functional properties with CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)1214-1229
Number of pages16
JournalJournal of Experimental Medicine
Volume216
Issue number5
DOIs
StatePublished - May 1 2019

PubMed: MeSH publication types

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

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    Beura, L. K., Fares-Frederickson, N. J., Steinert, E. M., Scott, M. C., Thompson, E. A., Fraser, K. A., Schenkel, J. M., Vezys, V., & Masopust, D. (2019). CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses. Journal of Experimental Medicine, 216(5), 1214-1229. https://doi.org/10.1084/jem.20181365