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.
Brewig
Nancy
N
Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Kissenpfennig
Adrien
A
Malissen
Bernard
B
Veit
Alexandra
A
Bickert
Thomas
T
Fleischer
Bernhard
B
Mostböck
Sven
S
Ritter
Uwe
U
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D003713:Dendritic Cells / Q000145:classification* / Q000276:immunology / Q000469:parasitology*; D004817:Epidermis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D005260:Female; D055879:Gene Knock-In Techniques / Q000379:methods; D007113:Immunity, Innate; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D037181:Lectins, C-Type / Q000235:genetics; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins