Migratory and antigen presentation functions of IFN-producing killer dendritic cells

Cancer Res. 2009 Aug 15;69(16):6598-606. doi: 10.1158/0008-5472.CAN-09-0501. Epub 2009 Aug 4.

Abstract

The CD11c(int) B220(+) NK1.1(+) CD49(+) subset of cells has recently been described as IFN-producing killer dendritic cells (IKDC), which share phenotypic and functional properties with both dendritic cells and natural killer cells. We have previously shown that IKDCs within murine bone marrow-derived DC preparations are essential for the antitumor activity of unpulsed DCs. Here we show that bone marrow-derived IKDCs (BM-IKDC) migrate in vivo into tumors and thence to tumor draining lymph nodes, where they highly express MHC class II and costimulatory molecules. In vitro, freshly isolated BM-IKDCs, fluorescence-activated cell sorted to homogeneity, have no intrinsic antigen presentation function unless cocultured with tumor target cells. On killing of target cells, they can cross-present antigens to stimulate antigen-primed CD8 T cells and can also present antigens to antigen-primed CD4 cells. In vivo, in mice lacking class I-restricted antigen-presenting cell function, robust proliferation of antigen-specific T cells is achieved after adoptive transfer of BM-IKDCs at an injection site distant to the tumor site. Therefore, BM-IKDCs are capable of cytotoxic killing of tumor targets and also of potent antigen presentation after encountering antigen in the context of a viable target cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Cell Movement* / immunology
  • Cells, Cultured
  • Cytotoxicity, Immunologic / physiology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / physiology*
  • Genes, RAG-1
  • Interferons / metabolism*
  • Melanoma, Experimental / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • NIH 3T3 Cells
  • beta 2-Microglobulin / genetics

Substances

  • beta 2-Microglobulin
  • Interferons