Directly Transfected Langerin+ Dermal Dendritic Cells Potentiate CD8+ T Cell Responses following Intradermal Plasmid DNA Immunization

Abstract

Material

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

“…Nevertheless, our data propose that the buccal mucosa and skin diverge when it comes to the role of particular DC subsets in T cell priming. In contrast to the buccal mucosa, we recently reported that LCs of the ear skin are dispensable for CD8 + T cell priming, whereas Ln + dDCs play a critical role during this process (23). Moreover, we showed that expression of plasmid DNA-encoded Ag in skin CD11c + cells is sufficient to prime CD8 + T cells, whereas in the current study restricting Ag expression to buccal-resident CD11c + cells resulted in diminished CD8 + T cell responses (23).…”

“…This, however, cannot explain the higher Ab titers in lining-immunized mice in which T cells were not affected by the ablation. Notably, the ability of LC to regulate Ab production but not T cell responses was also reported by us after intradermal plasmid DNA immunization (23). We thus suggest that LCs may have the ability to regulate Ab production in a T cell-independent manner.…”

“…In contrast to the buccal mucosa, we recently reported that LCs of the ear skin are dispensable for CD8 + T cell priming, whereas Ln + dDCs play a critical role during this process (23). Moreover, we showed that expression of plasmid DNA-encoded Ag in skin CD11c + cells is sufficient to prime CD8 + T cells, whereas in the current study restricting Ag expression to buccal-resident CD11c + cells resulted in diminished CD8 + T cell responses (23). Thus, the widespread comparison of buccal DCs and skin DCs is not always correct, and care should be taken in the future to avoid such assumption in other experimental systems.…”

“…Three days later, the cervical LNs were collected, processed, and CD11c + cells were enriched by magnetic bead-based positive selection. The cells were then stained with anti-CD11c, CD103, and Ep-CAM Abs to identify the various oral DC subsets based on their phenotype in the skin as previously described (23,40) Fig. 4A, buccal and lining migratory DCs were easily identified in the cervical LNs by FITC painting, whereas no FITC + cells were found in unpainted mice.…”

“…These studies also identified a new subset of DCs expressing langerin (Ln + dDCs), a receptor that was initially thought to be unique for LCs (18)(19)(20). Ln + dDCs present different origin and functional qualities than that of LCs and were found to mediate T cell priming in some experimental models (21)(22)(23). Nevertheless, whereas data are rapidly accumulating emphasizing the complexity of DC function in the body, DCs of the oral mucosa have been generally overlooked, and most of our knowledge of these cells is based on research of other tissues.…”