Dendritic cells in distinct oral mucosal tissues engage different mechanisms to prime CD8⁺ T cells

Although oral dendritic cells (DCs) were shown to induce cell-mediated immunity, the identity and function of the various oral DC subsets involved in this process is unclear. In this study, we examined the mechanisms used by DCs of the buccal mucosa and of the lining mucosa to elicit immunity. After plasmid DNA immunization, buccally immunized mice generated robust local and systemic CD8⁺ T cell responses, whereas lower responses were seen by lining immunization. A delayed Ag presentation was monitored in vivo in both groups; yet, a more efficient presentation was mediated by buccal-derived DCs. Restricting transgene expression to CD11c⁺ cells resulted in diminished CD8⁺ T cell responses in both oral tissues, suggesting that immune induction is mediated mainly by cross-presentation. We then identified, in addition to the previously characterized Langerhans cells (LCs) and interstitial dendritic cells (iDCs), a third DC subset expressing the CD103⁺ molecule, which represents an uncharacterized subset of oral iDCs expressing the langerin receptor (Ln⁺iDCs). Using Langerin-DTR mice, we demonstrated that whereas LCs and Ln⁺ iDCs were dispensable for T cell induction in lining-immunized mice, LCs were essential for optimal CD8⁺ T cell priming in the buccal mucosa. Buccal LCs, however, failed to directly present Ag to CD8⁺ T cells, an activity that was mediated by buccal iDCs and Ln⁺iDCs. Taken together, our findings suggest that the mechanisms engaged by oral DCs to prime T cells vary between oral mucosal tissues, thus emphasizing the complexity of the oral immune network. Furthermore, we found a novel regulatory role for buccal LCs in potentiating CD8⁺ T cell responses.