Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8⁺ T cell crosspriming in vivo

The nature of dendritic cell(s) (DC[s]) that conditions efficient in vivo priming of CD8⁺ CTL after immunization via epithelial tissues remains largely unknown. Here, we show that myeloid DCs rapidly recruited by adjuvants into the buccal mucosa or skin are essential for CD8⁺ T cell crosspriming. Recruitment of circulating DC precursors, including Gr1 ⁺ monocytes, precedes the sequential accumulation of CD11c ⁺ MHC class II⁺ DCs in dermis and epithelium via a CCR6/CCL20-dependent mechanism. Remarkably, a defect in CCR6, local neutralization of CCL20, or depletion of monocytes prevents in vivo priming of CD8⁺ CTL against an innocuous protein antigen administered with adjuvant. In addition, transfer of CCR6-sufficient Gr1⁺ monocytes restores CD8⁺ T cell priming in CCR6^°/° mice via a direct Ag presentation mechanism. Thus, newly recruited DCs likely derived from circulating monocytes are responsible for efficient crosspriming of CD8 ⁺ CTL after mucosal or skin immunization.