CD49a mediates cutaneous resident memory CD8+ T cell persistence and response

Abstract

Abstract Resident memory CD8+ T cells (TRM) persist at sites of previous infection where they provide rapid local protection against pathogen challenge. CD8+ TRM expressing the a1 chain (CD49a) of integrin VLA-1 have been identified within sites of resolved skin infection as well as in vitiligo lesions. This study examines the signals that regulate CD8+ T cell CD49a expression and its requirement for cutaneous TRM formation and response. We demonstrate that CD49a was expressed early following T cell activation in vivo, and that TGF-b as well as IL-12 induced CD49a expression by CD8+ T cells in vitro. Despite this rapid expression, CD49a was not required for the generation of a primary CD8+ T cell response to cutaneous herpes simplex virus (HSV) infection. Rather, CD49a mediated epidermal CD8+ TRM interaction with the extracellular matrix, supported CD8+ TRM persistence within the skin, and increased the frequency of CD8+ TRM that secrete IFN-g following local antigen challenge. Thus, our results suggest CD49a promotes optimal cutaneous CD8+ TRM-mediated immunity.