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 journalArticlepeer-review

91 Scopus citations


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
Issue number5
StatePublished - May 1 2019

Bibliographical note

Funding Information:
This work was funded by the Howard Hughes Medical Institute Faculty Scholars program and National Institutes of Health grants R01AI111671 and R01AI084913 (to D. Masopust). The authors declare no competing financial interests.

Publisher Copyright:
© 2019 Beura et al.


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