Integrin CD103 expression in naive CD8+ T cells promotes cytokine-driven acquisition of memory phenotype and effector function
Can Li, Davinna L. Ligons, Dominic Lanasa, Hilary R. Keller, Megan A. Luckey, Brian J. Capaldo, Daoud Meerzaman, Joo‐Young Park, Jung‐Hyun Park, Jung‐Hyun Park, Jung‐Hyun Park
Abstract
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.