Priming of CD8+ and CD4+ T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes

The biological role of Langerin + dendritic cells (DCs) such as Langerhans cells and a subset of dermal DCs (dDCs) in adaptive immunity against cutaneous pathogens remains enigmatic. Thus, we analyzed the impact of Langerin + DCs in adaptive T cell-mediated immunity toward Leishmania major parasites in a Lang-DTR mouse model that allows conditional diphtheria toxin (DT)-induced ablation of Langerin + DCs in vivo. For the first time, infection experiments with DT-treated Lang-DTR mice revealed that proliferation of L. major -specific CD8 + T cells is significantly reduced during the early phase of the immune response following depletion of Langerin + DCs. Consequently, the total number of activated CD8 + T cells within the draining lymph node and at the site of infection is diminished. Furthermore, we show that the impaired CD8 + T cell response is due to the absence of Langerin + dDCs and not Langerhans cells. Nevertheless, the CD4 + T cell response is not altered and the infection is cleared as effectively in DT-treated Lang-DTR mice as in control mice. This clearly demonstrates that Langerin + DCs are, in general, dispensable for an efficient adaptive immune response against L. major parasites. Thus, we propose a novel concept that, in the experimental model of leishmaniasis, priming of CD4 + T cells is mediated by Langerin − dDCs, whereas Langerin + dDCs are involved in early priming of CD8 + T cells.