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 alpha 1 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-beta 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-gamma(+) CD8(+) T-RM following local antigen challenge. Our results suggest that CD49a promotes optimal cutaneous CD8(+) T-RM-mediated immunity.