title: Dendritic cell maturation by CD11c- T cells and Valpha24+ natural killer T-cell activation by alpha-galactosylceramide.
abstract: Human invariant Valpha24+ natural killer T (NKT) cells display potent antitumor activity upon stimulation. Activation of endogenous Valpha24+ NKT cells would be one strategy for the treatment of cancer patients. For example, dendritic cells (DCs) loaded with a glycolipid NKT cell ligand, alpha-galactosylceramide (alphaGalCer, KRN7000), are a possible tool for the activation and expansion of functional Valpha24+ NKT cells in vivo. In this report, we demonstrate that the levels of expansion and the ability to produce IFN-gamma of Valpha24+ NKT cells induced by alphaGalCer-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 Valpha24+ NKT cells to enable them to produce IFN-gamma 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, CD11c-CD3+ T cells appeared to play important roles in DC maturation. In addition, TNF-alpha was preferentially produced by CD11c-CD3+ 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-alpha production appears to result in the efficient expansion and activation of Valpha24+ NKT cells to produce IFN-gamma preferentially.
authors.affiliation: Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Aki
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ito
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Uchida
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kaneko
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Koji
authors.initials: K
authors.lastname: Tsuboi
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsumura
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology; D005699:Galactosylceramides / Q000494:pharmacology*; D014644:Genetic Variation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D039521:CD11c Antigen; D005699:Galactosylceramides; D007376:Interleukin-2; C493154:alpha-galactosylceramide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor