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Dendritic cell maturation by CD11c − T cells and Vα24 + natural killer T‐cell activation by α‐Galactosylceramide
Author(s) -
Ishikawa Eiichi,
Motohashi Shinichiro,
Ishikawa Aki,
Ito Toshihiro,
Uchida Tetsuro,
Kaneko Takaaki,
Tanaka Yuriko,
Horiguchi Shigetoshi,
Okamoto Yoshitaka,
Fujisawa Takehiko,
Tsuboi Koji,
Taniguchi Masaru,
Matsumura Akira,
Nakayama Toshinori
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21197
Subject(s) - natural killer t cell , cd11c , t cell , microbiology and biotechnology , cd8 , dendritic cell , cytokine , biology , peripheral blood mononuclear cell , antigen presenting cell , immunology , chemistry , immune system , in vitro , phenotype , biochemistry , gene
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, CD11c − CD3 + T cells appeared to play important roles in DC maturation. In addition, TNF‐α 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‐α production appears to result in the efficient expansion and activation of Vα24 + NKT cells to produce IFN‐γ preferentially. © 2005 Wiley‐Liss, Inc.