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.