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

Brewig, Nancy and Kissenpfennig, Adrien and Malissen, Bernard and Veit, Alexandra and Bickert, Thomas and Fleischer, Bernhard and Mostboeck, Sven and Ritter, Uwe (2009) Priming of CD8(+) and CD4(+) T Cells in Experimental Leishmaniasis Is Initiated by Different Dendritic Cell Subtypes. JOURNAL OF IMMUNOLOGY, 182 (2). pp. 774-783. ISSN 0022-1767,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: EPIDERMAL LANGERHANS CELLS; REAL-TIME PCR; LYMPH-NODE; IN-VIVO; CONTACT HYPERSENSITIVITY; CUTANEOUS LEISHMANIASIS; IMMUNOLOGICAL MEMORY; IMMUNE-RESPONSE; MAJOR INFECTION; MICE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Immunologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 07 Oct 2020 09:16
Last Modified: 07 Oct 2020 09:16
URI: https://pred.uni-regensburg.de/id/eprint/29578

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