Enhanced Gamma Interferon Production through Activation of Vα14<sup><i>+</i></sup>Natural Killer T Cells by α-Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis
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- Kazuyoshi Kawakami
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Yuki Kinjo
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Satomi Yara
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Kaori Uezu
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Yoshinobu Koguchi
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Masaki Tohyama
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Masato Azuma
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- Kiyoshi Takeda
- <!--label omitted: 2-->Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka,2 Japan
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- Shizuo Akira
- <!--label omitted: 2-->Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka,2 Japan
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- Atsushi Saito
- <!--label omitted: 1-->First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa,1 and
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- S. H. E. Kaufmann
- editor
抄録
<jats:title>ABSTRACT</jats:title><jats:p>We showed recently that activation of Vα14<jats:sup>+</jats:sup>natural killer T cells (NKT cells) by α-galactosylceramide (α-GalCer) resulted in increased gamma interferon (IFN-γ) production and host resistance to intravenous infection with<jats:italic>Cryptococcus neoformans</jats:italic>. In other studies, interleukin-18 (IL-18) activated NKT cells in collaboration with IL-12, suggesting the possible contribution of this cytokine to α-GalCer-induced IFN-γ synthesis. Here we examined the role of IL-18 in α-GalCer-induced Th1 response by using IL-18KO mice with this infection. In these mice, levels of IFN-γ in serum and its synthesis in vitro by spleen cells stimulated with live organisms were not reduced, but rather enhanced, compared to those in wild-type (WT) mice, while such production was completely absent in IL-12KO mice. The enhanced production of IFN-γ correlated with increased IL-12 synthesis but not with reduced production of IL-4, which was rather increased. IFN-γ synthesis in IL-18KO mice was abolished by neutralizing anti-IL-12 antibody and significantly inhibited by neutralization of endogenous IL-4 with a specific monoclonal antibody. In addition, administration of recombinant IL-4 significantly enhanced the production of IFN-γ in WT mice. Finally, the enhanced production of IFN-γ in IL-18KO mice correlated with increased host defense against cryptococcal infection, as indicated by enhancement in α-GalCer-related clearance of microorganisms. Our results indicated that in IL-18KO mice, IFN-γ synthesis was enhanced through overproduction of IL-12 and IL-4 after intravenous infection with<jats:italic>C. neoformans</jats:italic>and a ligand-specific activation of Vα14<jats:sup>+</jats:sup>NKT cells.</jats:p>
収録刊行物
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- Infection and Immunity
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Infection and Immunity 69 (11), 6643-6650, 2001-11
American Society for Microbiology
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詳細情報 詳細情報について
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- CRID
- 1362262945526569600
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- NII論文ID
- 30020828960
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- ISSN
- 10985522
- 00199567
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- データソース種別
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