Human CD1c+ Dendritic Cells Drive the Differentiation of CD103+ CD8+ Mucosal Effector T Cells via the Cytokine TGF-β

In comparison to murine dendritic cells (DCs), less is known about the function of human DCs in tissues. Here, we analyzed, by using lung tissues from humans and humanized mice, the role of human CD1c+ and CD141+ DCs in determining the type of CD8+ T cell immunity generated to live-attenuated influenza virus (LAIV) vaccine. We found that both lung DC subsets acquired influenza antigens in vivo and expanded specific cytotoxic CD8+ T cells in vitro. However, lung-tissue-resident CD1c+ DCs, but not CD141+ DCs, were able to drive CD103 expression on CD8+ T cells and promoted CD8+ T cell accumulation in lung epithelia in vitro and in vivo. CD1c+ DCs induction of CD103 expression was dependent on membrane-bound cytokine TGF-β1. Thus, CD1c+ and CD141+ DCs generate CD8+ T cells with different properties, and CD1c+ DCs specialize in the regulation of mucosal CD8+ T cells. ► CD1c+ and CD141+ DC subsets populate human lungs and the lungs of humanized mice ► Both DCs acquire influenza antigens in vivo and expand specific CD8+ T cells ► Human CD1c+ DCs expand CD103+CD8+ mucosal T cells in vitro and in vivo ► CD1c+ DCs expand CD103+CD8+ T cells via membrane-bound TGF-β.