CD49a Regulates Cutaneous Resident Memory CD8(+) T Cell Persistence and Response

CD8(+) tissue-resident memory T cells (T(RM)) persist at sites of previous infection, where they provide rapid local protection against pathogen challenge. CD8(+) T(RM) expressing the α1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection and in vitiligo lesions. We demonstrate that CD49a is expressed early following T cell activation in vivo, and TGF-β and IL-12 induce CD49a expression by CD8(+) T cells in vitro. Despite this rapid expression, CD49a is not required for the generation of a primary CD8(+) T cell response to cutaneous herpes simplex virus (HSV) infection, migration of CD8(+) T cells across the epidermal basement membrane, or positioning of T(RM) within basal epidermis. Rather, CD49a supports CD8(+) T(RM) persistence within skin, regulates epidermal CD8(+) T(RM) dendritic extensions, and increases the frequency of IFN-γ(+) CD8(+) T(RM) following local antigen challenge. Our results suggest that CD49a promotes optimal cutaneous CD8(+) T(RM)-mediated immunity.