Integrin CD103 expression in naive CD8

Integrin CD103 binds to E-cadherin, a cell adhesion molecule predominantly expressed on epithelial cells, thus mediating the tissue residency of CD103+ T cells in barrier sites. Importantly, circulating naive CD8+ T cells also express large amounts of CD103, but whether CD103 contributes to CD8+ T cell immunity beyond its role in cell adhesion is unclear. Here, we report that CD103 expression in naive CD8+ T cells facilitates their engagement with E-cadherin-expressing cells, promoting their acquisition of memory phenotype and effector function. Notably, dendritic cell (DC) subsets expressing E-cadherin and producing type I interferons and interleukin-12 (IL-12) were responsible for this process. As a corollary, the DC-specific loss of E-cadherin resulted in diminished effector CD8+ T cell differentiation and increased tumor susceptibility, while the forced expression of CD103 enhanced the effector functions and anti-tumor activity of CD8+ T cells, revealing a regulatory role for CD103 in cytotoxic T cell immunity.