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 CCRo/o 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.
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