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(+) Ms. 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. The Journal of Immunology, 2009, 182: 774-783.