Central memory T (TCM) cells patrol lymph nodes and perform conventional memory responses on restimulation: proliferation, migration and differentiation into diverse T cell subsets while also self-renewing. Resident memory T (TRM) cells are parked within single organs, share properties with terminal effectors and contribute to rapid host protection. We observed that reactivated TRM cells rejoined the circulating pool. Epigenetic analyses revealed that TRM cells align closely with conventional memory T cell populations, bearing little resemblance to recently activated effectors. Fully differentiated TRM cells isolated from small intestine epithelium exhibited the potential to differentiate into TCM cells, effector memory T cells and TRM cells on recall. Ex-TRM cells, former intestinal TRM cells that rejoined the circulating pool, heritably maintained a predilection for homing back to their tissue of origin on subsequent reactivation and a heightened capacity to redifferentiate into TRM cells. Thus, TRM cells can rejoin the circulation but are advantaged to re-form local TRM when called on.
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We thank the members of the Masopust laboratory and the University of Minnesota Center for Immunology for helpful discussions. We were funded by a National Institutes of Health grant (no. R01AI084913), the Howard Hughes Medical Institute Scholars program (to D.M.) and an FAPESP-BEPE (2015/00680-7) fellowship (to R.F).
The authors declare no competing interests.
Peer review information Z. Fehervari was the primary editor on this article, and managed its editorial process and peer review in collaboration with the rest of the editorial team.
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Fonseca, R., Beura, L.K., Quarnstrom, C.F. et al. Developmental plasticity allows outside-in immune responses by resident memory T cells. Nat Immunol 21, 412–421 (2020). https://doi.org/10.1038/s41590-020-0607-7
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