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The Dendritic Cell–like Functions of IFN-Producing Killer Dendritic Cells Reside in the CD11b⁺ Subset and Are Licensed by Tumor Cells

¹ Institut National de la Sante et de la Recherche Medicale, U805; ² Institut Gustave Roussy; ³ Université Paris-Sud, Villejuif, France; ⁴ Department of Immunology, Duke University Medical Center, Durham, North Carolina; ⁵ Center of Clinical Investigations, CBT507, IGR/Curie, Villejuif/Paris, France; ⁶ Laboratory for Genomics and Immunoregulation, LIMES Institute, University of Bonn, Bonn, Germany; ⁷ Institut National de la Sante et de la Recherche Medicale, U848, Villejuif, France; ⁸ Unit of Biology of Immune Regulations, Institut Pasteur; and ⁹ Institut National de la Sante et de la Recherche Medicale, U 883, Paris, France

Requests for reprints: Laurence Zitvogel, U805 and CIC BT507 Institut National de la Sante et de la Recherche Medicale, Institut Gustave Roussy, 39 rue Camille Desmoulins, F-94805 Villejuif, France. Phone: 33-1-42-11-50-41; Fax: 33-1-42-11-60-94; E-mail: zitvogel{at}igr.fr.

Key Words: IKDC • antigen presentation • tumor cells

IFN producing killer dendritic cells (IKDC) were originally defined as CD11c^int B220⁺NK1.1⁺ (or CD49b⁺) cells that exert a potent tumoricidal activity in animals lacking B, T, and conventional natural killer effectors. MHC class II expression on tumor infiltrating IKDC prompted us to investigate their putative antigen presenting function. Here, we show that tumor cells license IKDC to acquire the properties of antigen presenting cells, i.e., expression of MHC class II and costimulatory CD86 molecules. We show that the CD11b⁺ subset of IKDC are able to prime naïve CD4⁺ T cells and cross-prime naïve CD8⁺ T lymphocytes. Licensing of IKDC by tumor cells was mandatory for the full differentiation of T cells into polarized effectors. IKDC could engulf and process soluble Ova protein in a CD206-dependent manner. Finally, we show that CD11b⁺IKDC is selectively endowed with CTLA4Ig-inhibitable antigen presenting capacities and that targeting this subset with the detoxified adenylate cyclase toxin of Bordetella pertussis fused to antigen resulted in efficient cross-presentation of antigen by IKDC to specific TCR transgenic CD8⁺T cells in vivo. Collectively, our data indicate that upon exposure to tumor cells, IKDC subserve DC-like functions. [Cancer Res 2009;69(16):6590–7]

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