The Role of Skin-Derived Dendritic Cells in CD8+ T Cell Priming Following Immunization with Lentivectors

Abstract

Although skin dendritic cells (DCs) have been shown to directly present Ag to CD8+ T cells after intradermal immunization with lentivectors, the contribution of the different skin DC subsets to this process remains unclear. Using langerin-diphtheria toxin receptor transgenic mice we demonstrated that ablation of langerhans cells and langerin-expressing positive dermal DCs (Ln+dDCs) did not interfere with the generation of CD8+ T cells by lentiviral vectors. Consistent with these findings, the absence of langerhans cells and Ln+dDCs did not hamper the presentation level of lentiviral-derived Ag by skin DCs in vitro. We further demonstrated that only dDCs and Ln+dDCs were capable of presenting Ag, however, the number of dDCs migrating to the draining lymph nodes was 6-fold higher than that of Ln+dDCs. To study how the duration of DC migration influences CD8+ T cell responses, we analyzed the kinetics of Ag expression at the injection site and manipulated DC migration by excising the injected skin at various times after immunization. A low level of Ag expression was seen 1 wk after the immunization; peaked during week 2, and was considerably cleared by week 3 via a perforin-dependent fas-independent mechanism. Removing the injection site 3 or 5 d, but not 10 d, after the immunization, resulted in a reduced CD8+ T cell response. These findings suggest that dDCs are the main APCs active after intradermal lentiviral-mediated immunization, and migration of dDCs in the initial 10-d period postimmunization is required for optimal CD8+ T cell induction.