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Migratory and Antigen Presentation Functions of IFN-Producing Killer Dendritic Cells

¹ Unit of Molecular Haematology and Cancer Biology, ² Unit of Molecular Immunology, and ³ Flow Cytometry Core Facility, University College London Institute of Child Health; ⁴ National Institute of Medical Research; and ⁵ Department of Paediatric Oncology, Great Ormond Street Hospital, London, United Kingdom

Requests for reprints: John Anderson, Unit of Molecular Haematology and Cancer Biology, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom. Phone: 44-207-905-2265; Fax: 44-207-813-8100; E-mail: j.anderson{at}ich.ucl.ac.uk.

Key Words: IKDC • NK • dendritic cell • cancer

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. [Cancer Res 2009;69(16):6598–606]

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