Dendritic cell maturation by CD11c- T cells and Valpha24+ natural killer T-cell activation by alpha-galactosylceramide.
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.
Ishikawa
Eiichi
E
Department of Neurosurgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Motohashi
Shinichiro
S
Ishikawa
Aki
A
Ito
Toshihiro
T
Uchida
Tetsuro
T
Kaneko
Takaaki
T
Tanaka
Yuriko
Y
Horiguchi
Shigetoshi
S
Okamoto
Yoshitaka
Y
Fujisawa
Takehiko
T
Tsuboi
Koji
K
Taniguchi
Masaru
M
Matsumura
Akira
A
Nakayama
Toshinori
T
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*
D015703:Antigens, CD; D039521:CD11c Antigen; D005699:Galactosylceramides; D007376:Interleukin-2; C493154:alpha-galactosylceramide; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor