PD-1 is requisite for skin T_RM cell formation and specification by TGFβ

Tissue-resident memory T (T_RM) cells provide infectious, cancer and vaccine-trained immunity across barrier sites. T_RM cells are implicated in autoimmunity, successful response to immune checkpoint blockade in the tumor microenvironment and toxicities that occur after immune checkpoint blockade in peripheral tissues. Here, we identified that signaling through the immune checkpoint programmed death receptor 1 (PD-1) strongly impacts the early specification of CD8⁺ T_RM cells in the skin. PD-1 is expressed broadly across mouse and human skin T_RM cells, in the absence of persistent infection, and is retained on skin T_RM cells in aged mice. PD-1 supports early T_RM cell colonization, skin-specific programming and silencing of other differentiation programs and promotes TGFβ responsivity and skin engraftment. Thus, PD-1 signaling mediates skin T_RM cell specification during immune initiation. These findings may inform therapeutic PD-1 agonist and antagonist use to modulate successful peripheral memory.