Dendritic cell maturation by CD11c T cells and Vα24+ natural killer T-cell activation by α-Galactosylceramide

Authors

  • Eiichi Ishikawa,

    1. Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan
    2. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Shinichiro Motohashi,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
    2. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Aki Ishikawa,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
    2. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Toshihiro Ito,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Tetsuro Uchida,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
    2. Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Takaaki Kaneko,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Yuriko Tanaka,

    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
    2. Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Shigetoshi Horiguchi,

    1. Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Yoshitaka Okamoto,

    1. Department of Otorhinolaryngology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Takehiko Fujisawa,

    1. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
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  • Koji Tsuboi,

    1. Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan
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  • Masaru Taniguchi,

    1. Laboratory for Immune Regulation, Riken Research Center for Allergy and Immunology, Yokohama, Japan
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  • Akira Matsumura,

    1. Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan
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  • Toshinori Nakayama

    Corresponding author
    1. Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan
    • Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
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    • Fax: +81-43-227-1498.


Abstract

Human invariant Vα24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Vα24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, α-galactosylceramide (αGalCer, KRN7000), are a possible tool for the activation and expansion of functional Vα24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN-γ of Vα24+ NKT cells induced by αGalCer-loaded whole PBMCs cultured with IL-2 and GM-CSF (IL-2/GM-CSF-cultured PBMCs) were superior to those of cells induced by monocyte-derived CD11c+ DCs (moDCs) developed with IL-4 and GM-CSF. Interestingly, CD11c+ cells in the IL-2/GM-CSF-cultured PBMCs showed a mature phenotype without further stimulation and exerted potent stimulatory activity on Vα24+ NKT cells to enable them to produce IFN-γ preferentially at an extent equivalent to mature moDCs induced by stimulation with LPS or a cytokine cocktail. Cocultivation with CD11c cells in the IL-2/GM-CSF-cultured PBMCs induced maturation of moDCs. In particular, CD11cCD3+ T cells appeared to play important roles in DC maturation. In addition, TNF-α was preferentially produced by CD11cCD3+ T cells in IL-2/GM-CSF-cultured PBMCs and was involved in the maturation of moDCs. Thus, the maturation of DCs induced by CD11c T cells through TNF-α production appears to result in the efficient expansion and activation of Vα24+ NKT cells to produce IFN-γ preferentially. © 2005 Wiley-Liss, Inc.

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