CD70-CD27 interaction augments CD8 T-cell activation by human epidermal langerhans cells

Abstract

Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4 T-cell and humoral immune responses; however, differences in the regulation of memory CD8 T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8 cells. Although tumor necrosis factor-α-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8 cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8 epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8 T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8 activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8 cells by LCs denotes a central role of LCs in CD8 immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer. © 2012 The Society for Investigative Dermatology.