Natural killer dendritic cells are an intermediate of developing dendritic cells

J Leukoc Biol. 2007 Jun;81(6):1422-33. doi: 10.1189/jlb.1106674. Epub 2007 Mar 1.

Abstract

NK dendritic cells (DCs; NKDCs) appear to emerge as a distinct DC subset in humans and rodents, which have the functions of NK cells and DCs. However, the developmental relationship of NKDCs (CD11c(+)NK1.1(+)) to CD11c(+)NK1.1(-) DCs has not been addressed. Herein, we show that NKDCs exist exclusively in the compartment of CD11c(+)MHC II(-) cells in the steady state and express variable levels of DC subset markers, such as the IFN-producing killer DC marker B220, in a tissue-dependent manner. They can differentiate into NK1.1(-) DCs, which is accompanied by the up-regulation of MHC Class II molecules and down-regulation of NK1.1 upon adoptive transfer. However, NK cells (NK(+)CD11c(-)) did not differentiate into NK1.1(+)CD11c(+) cells upon adoptive transfer. Bone marrow-derived Ly6C(+) monocytes can be a potential progenitor of NKDCs, as some of them can differentiate into CD11c(+)NK1.1(+) as well as CD11c(+)NK1.1(-) cells in vivo. The steady-state NKDCs have a great capacity to lyse tumor cells but little capability to present antigens. Our studies suggest that NKDCs are an intermediate of developing DCs. These cells appear to bear the unique surface phenotype of CD11c(+)NK1.1(+)MHC II(-) and possess strong cytotoxic function yet show a poor ability to present antigen in the steady state. These findings suggest that NKDCs may play a critical role in linking innate and adaptive immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • CD11c Antigen / immunology*
  • Cell Differentiation
  • Cell Line
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Proliferation
  • Cell Survival
  • Cytotoxicity, Immunologic
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Immunity, Active
  • Immunity, Innate
  • Killer Cells, Natural / cytology*
  • Killer Cells, Natural / immunology
  • Leukocyte Common Antigens / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Monocytes / immunology

Substances

  • CD11c Antigen
  • Histocompatibility Antigens Class II
  • Leukocyte Common Antigens