Dendritic Cells in Distinct Oral Mucosal Tissues Engage Different Mechanisms To Prime CD8+ T Cells

Abstract

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.

Intradermal Immunization Triggers Epidermal Langerhans Cell Mobilization Required for CD8 T-Cell Immune Responses

“…In addition, both LCs and CD207 þ DDCs would be involved in contact hypersensitivity depending on the hapten dose (Kaplan et al, 2005;Bennett et al, 2007;Honda et al, 2010;Noordegraaf et al, 2010). Eventually, Nudel et al (2011) proved the crucial role of LCs in the induction of CD8 T cells after an oral mucosal immunization. Indeed, the nature of the vaccine preparation or of the pathogen, as well as the antigen dose and the route of administration, are important parameters that could influence the differential involvement of LCs or CD207 þ DCs for the induction of immune responses.…”

Variation and significance of secretory immunoglobulin A, interleukin 6 and dendritic cells in oral cancer

“…Immune status has been revealed to serve an important role in interfering with tumor progression, and dendritic cells (DCs), the most efficient type of antigen presenting cells, have become the focus of investigation into immune regulation (4). The regulatory cytokines of DCs, such as interleukin (IL)-6, IL-2 and IL-10, serve important roles in maintaining mucosal homeostasis (5). …”

DNA Vaccines for the Induction of Immune Responses in Mucosal Tissues

“…In contrast, targeting the DNA vaccine to the anterior labial mucosa was less effective in inducing CD8 + T cells, and the most efficient antigen presentation was mediated by buccal-derived CD11c + DCs that are capable of antigen cross-presentation. Interestingly, although Langerhans cells are indispensable for CD8 + T cell induction after buccal immunization, direct DC targeting of DNA vaccines seems to be effective only via interstitial DCs or interstitial CD103 + langerin + DCs, because Langerhans cells do not directly present antigens to CD8 T cells (Nudel et al, 2011). This observation highlights the need for deeper understanding of mucosal immunity to design mucosally delivered DNA vaccines effectively.…”