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Immunology |
1 Sidney Kimmel Comprehensive Cancer Center and 2 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; 3 Department of Cell Biology and Human Anatomy, UC Davis School of Medicine, Davis, California; and 4 Microbiology and Immunology, School of Biomedical and Chemical Sciences, University of Western Australia, Crawley, Western Australia
Requests for reprints: Franck Housseau, Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, CRB-I Room 4M59, 1650 Orleans Street, Baltimore, MD 21231. Phone: 410-502-9846; Fax: 410-614-0549; E-mail: fhousse1{at}jhmi.edu.
Key Words: antigen presentation dendritic cells natural killer
IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, interleukin (IL)-12, natural killing, and ultimately antigen presentation to naïve T cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells (DC), and natural killer (NK) cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-
, but unlike NK, IKDC simultaneously produced IL-12p40 and up-regulated MHC class II (MHC-II) and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further showed that highly purified MHC-II+ IKDC but not NK cross-present MHC class I–restricted antigens derived from MCMV-infected targets to CD8+ T cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen-presenting cell directly linking innate and adaptive immunity. [Cancer Res 2009;69(16):6607–14]
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N. Himoudi, M. Yan, G. Bouma, D. Morgenstern, R. Wallace, B. Seddon, J. Buddle, A. Eddaoudi, S. J. Howe, N. Cooper, et al. Migratory and Antigen Presentation Functions of IFN-Producing Killer Dendritic Cells Cancer Res., August 15, 2009; 69(16): 6598 - 6606. [Abstract] [Full Text] [PDF] |
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