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Priming of CD8⁺ and CD4⁺ T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes¹

Nancy Brewig^*, Adrien Kissenpfennig, Bernard Malissen, Alexandra Veit^*, Thomas Bickert^*, Bernhard Fleischer^*, Sven Mostböck and Uwe Ritter^2,*,

^* Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; Centre for Infection and Immunity, School of Medicine, Dentistry & Biomedical Sciences, School of Biomedical Sciences, Queens University Belfast, United Kingdom; Centre d’Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique, Marseille, France; and Department of Immunology, University of Regensburg, Regensburg, Germany

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Jung Foundation of Science and Research, Hamburg and the Germany Research Foundation (Deutsche Forschungsgemeinschaft, RI 1849/1-1).

² Address correspondence and reprint requests to Dr. Uwe Ritter, Department of Immunology, University of Regensburg, Franz-Josef-Strauss-Allee-11, Regensburg, Germany. E-mail address: uwe.ritter{at}klinik.uni-regensburg.de

³ Abbreviations used in this paper: DC, dendritic cell; dDC, dermal DC; LC, Langerhans cell; DT, diphtheria toxin; SLA, soluble Leishmania Ag; SDLN, skin-draining LN; LN, lymph node; DTH, delayed-type hypersensitivity.

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