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Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells¹

Nourredine Himoudi^*, Stephen Nabarro^*, Jo Buddle, Ayad Eddaoudi, Adrian J. Thrasher and John Anderson^2,*

^* Unit of Molecular Haematology and Cancer Biology and Unit of Molecular Immunology, Institute of Child Health, London, United Kingdom

The CD11c^intB220⁺NK1.1⁺CD49⁺ subset of cells has recently been described as IFN-producing killer dendritic cells (IKDC), which share phenotypic and functional properties of dendritic cells and NK cells. Herein we show that bone marrow-derived murine dendritic cell preparations contain abundant CD11c^intB220⁺NK1.1⁺CD49⁺ cells, the removal of which results in loss of tumoricidal activity of unpulsed dendritic cells in vivo. Moreover, following s.c. injection, as few as 5 x 10³ highly pure bone marrow-derived IKDC cells are capable of shrinking small contralateral syngeneic tumors in C57BL/6 mice, but not in immunodeficient mice, implying the obligate involvement of host effector cells in tumor rejection. Our data suggest that bone marrow-derived IKDC represent a population that has powerful tumoricidal activity in vivo.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by research grants from SPARKS (Sport Aiding Medical Research in Kids), Cancer Research UK, and RICC (Research into Childhood Cancer).

² Address correspondence and reprint requests to Dr. John Anderson, Unit of Molecular Haematology and Cancer Biology, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom. E-mail address: j.anderson{at}ich.ucl.ac.uk

³ Abbreviations used in this paper: DC, dendritic cell; BM-IKDC, bone marrow-derived IKDC; CTL, cytotoxic lymphocyte; IKDC, IFN-producing killer dendritic cells; MTS, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt; pDC, plasmacytoid DC; rm, recombinant murine.

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