Epidermal Resident Memory T Cell Fitness Requires Antigen Encounter in the Skin
Abstract
CD8+tissue resident memory T cells (TRM) develop from effectors that seed peripheral tissues where they persist providing defense against subsequent challenges. TRMpersistence requires autocrine TGFβ transactivated by integrins expressed on keratinocytes. TRMprecursors that encounter antigen in the epidermis during development outcompete bystander TRMfor TGFβ resulting in enhanced persistence. ScRNA-seq analysis of epidermal TRMrevealed that local antigen experience in the skin resulted in an enhanced differentiation signature in comparison with bystanders. Upon recall, TRMdisplayed greater proliferation dictated by affinity of antigen experienced during epidermal development. Finally, local antigen experienced TRMdifferentially expressed TGFβRIII, which increases avidity of the TGFβRI/II receptor complex for TGFβ. Selective ablation ofTgfbr3reduced local antigen experienced TRMcapacity to persist, rendering them phenotypically like bystander TRM. Thus, antigen driven TCR signaling in the epidermis during TRMdifferentiation results in a lower TGFβ requirement for persistence and increased proliferative capacity that together enhance epidermal TRMfitness.
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