Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites

SUMMARY

Tissue-resident memory T cells (TRM) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRM remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells comprise a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69 ⁺ subset of memory CD4 ⁺ and CD8 ⁺ T cells in lung and spleen that is distinct from that of CD69 ⁻TEM cells in tissues and circulation, and defines human TRM based on homology to the transcriptional profile of mouse CD8 ⁺TRM. Human TRM in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced proliferation compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.

eTOC Blurb

Kumar et al. identify a core transcriptional and phenotypic signature which defines human TRM for both CD4 ⁺ and CD8 ⁺ T cells that is preserved across diverse individuals and in mucosal and lymphoid sites.