Priming of CD8+ and CD4+ T cells in experimental leishmaniasis is initiated by different dendritic cell subtypes

J Immunol. 2009 Jan 15;182(2):774-83. doi: 10.4049/jimmunol.182.2.774.

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+ 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / genetics
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / parasitology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / parasitology*
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology
  • Dendritic Cells / parasitology*
  • Epidermis / immunology
  • Epidermis / metabolism
  • Epidermis / parasitology
  • Female
  • Gene Knock-In Techniques / methods
  • Immunity, Innate
  • Langerhans Cells / immunology
  • Langerhans Cells / metabolism
  • Langerhans Cells / parasitology
  • Lectins, C-Type / genetics
  • Leishmania major / immunology
  • Leishmaniasis, Cutaneous / immunology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Lymph Nodes / parasitology
  • Lymph Nodes / pathology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Mannose-Binding Lectins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic

Substances

  • Antigens, Surface
  • Cd207 protein, mouse
  • Lectins, C-Type
  • Mannose-Binding Lectins