Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 216, Issue 5, Pages 1214-1229Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20181365
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Funding
- Howard Hughes Medical Institute Faculty Scholars program
- National Institutes of Health [R01AI111671, R01AI084913]
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This study examines the extent to which memory CD4(+) T cells share immunosurveillance strategies with CD8(+) resident memory T cells (T-RM). 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(+) T-RM 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(+) T-RM 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.
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