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J Exp Med. 2019 May 6;216(5):1214-1229. doi: 10.1084/jem.20181365. Epub 2019 Mar 28.

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

Author information

1
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN.
2
Center for Immunology, University of Minnesota, Minneapolis, MN.
3
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN masopust@umn.edu.

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.

PMID:
30923043
PMCID:
PMC6504216
[Available on 2019-11-06]
DOI:
10.1084/jem.20181365

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