Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo

Abstract

Dendritic cells (DCs) are composed of multiple subsets that play a dual role in inducing immunity and tolerance. However, it is unclear how CD205 + conventional DCs (cDCs) control immune responses in vivo. Here we generated knock-in mice with the selective conditional ablation of CD205 + cDCs. CD205+ cDCs contributed to antigenspecific priming of CD4+ T cells under steady-state conditions, whereas they were dispensable for antigen-specific CD4+ T-cell responses under inflammatory conditions. In contrast, CD205+cDCs were required for antigen-specific priming of CD8+ T cells to generate cytotoxic T lymphocytes (CTLs) mediated through crosspresentation. Although CD205 + cDCs were involved in the thymic generation of CD4+ regulatory T cells (Tregs), they maintained the homeostasis of CD4+ Tregs and CD4+ effector T cells in peripheral andmucosal tissues. On the other hand, CD205+ cDCs were involved in the inflammation triggered by Toll-like receptor ligand as well as bacterial and viral infections. Upon microbial infections, CD205+cDCs contributed to the cross-priming of CD8+ T cells for generating antimicrobial CTLs to efficiently eliminate pathogens, whereas they suppressed antimicrobial CD4 + T-cell responses. Thus, these findings reveal a critical role for CD205+ cDCs in the regulation of T-cell immunity and homeostasis in vivo.