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

摘要

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 antigen-specific 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 cross-presentation. 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 and mucosal tissues. On the other hand, CD20V 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.