Keratinocyte-mediated activation of the cytokine TGFβ maintains skin-recirculating memory CD8(+) T cells

Regulated activation of the cytokine TGFβ by integrins α(v)β(6) and α(v)β(8) expressed on keratinocytes is required for residence of epidermal-resident memory T cells, but whether skin-derived signals also affect recirculating memory cells in the skin remains unclear. Here, we show that after resolution of skin vaccinia virus (VV) infection, antigen-specific circulating memory CD8(+) T cells migrated into skin. In mice lacking α(v)β(6) and α(v)β(8) integrins (Itgb6(−/−)Itgb8(fl/fl)-K14-cre), the absence of epidermal activated TGFβ resulted in a gradual loss of E- or P-selectin-binding central and peripheral memory populations, that was rescued when skin entry was inhibited. Skin recirculating memory cells were required for optimal host defense against skin VV infection. These data demonstrate that skin migration can persist after resolution of local skin infection and that the cytokine environment within this nonlymphoid tissue shapes the differentiation state and persistence of the central and peripheral memory T cell pool.