CD103 Preconditions Naïve CD8 T Cells for Their Acquisition of Effector Phenotype and Function

Abstract

Integrin CD103 binds to E-cadherin, a cell adhesion protein predominantly expressed on epithelial cells, thus mediating the tissue-residency of CD103+ T cells in barrier tissues. Notably, naïve CD8 T cells circulating through lymphoid organs also express copious amounts of CD103. However, it has been unclear whether and what roles CD103 would play for CD8 T cells outside of barrier sites. Here, we unveil a previously unappreciated role of CD103 in preconditioning naïve CD8 T cells for their effector-memory differentiation, and we further identify a new subset of lymph node dendritic cells that express E-cadherin (E-cad+ DCs) and produce IFN-β and IL-12, being responsible for this process. As a corollary, the lack of E-cad+ DCs resulted in diminished effector CD8 T cell differentiation and increased tumor susceptibility while the forced expression of CD103 markedly bolstered the effector functions and anti-tumor activity of CD8 T cells, revealing a regulatory role for CD103 in cytotoxic T cell immunity.

Keywords: Dendritic cells, E-cadherin, IFN-β, IL-12, IL-15