Interleukin (IL)-18 synergizes with IL-12 to promote T helper cell (Th)1 responses. Somewhat paradoxically, IL-18 administration alone strongly induces immunoglobulin (Ig)E production and allergic inflammation, indicating a role for IL-18 in the generation of Th2 responses. The ability of IL-18 to induce IgE is dependent on CD4+ T cells, IL-4, and signal transducer and activator of transcription (stat)6. Here, we show that IL-18 fails to induce IgE both in CD1d−/− mice that lack natural killer T (NKT) cells and in class II−/− mice that lack conventional CD4+ T cells. However, class II−/− mice reconstituted with conventional CD4+ T cells show the capacity to produce IgE in response to IL-18. NKT cells express high levels of IL-18 receptor (R)α chain and produce significant amounts of IL-4, IL-9, and IL-13, and induce CD40 ligand expression in response to IL-2 and IL-18 stimulation in vitro. In contrast, conventional CD4+ T cells express low levels of IL-18Rα and poorly respond to IL-2 and IL-18. Nevertheless, conventional CD4+ T cells are essential for B cell IgE responses after the administration of IL-18. These findings indicate that NKT cells might be the major source of IL-4 in response to IL-18 administration and that conventional CD4+ T cells demonstrate their helper function in the presence of NKT cells.
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21 April 2003
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April 14 2003
Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice
Tomohiro Yoshimoto,
Tomohiro Yoshimoto
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Booki Min,
Booki Min
3Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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Takaaki Sugimoto,
Takaaki Sugimoto
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Nobuki Hayashi,
Nobuki Hayashi
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Yuriko Ishikawa,
Yuriko Ishikawa
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Yuki Sasaki,
Yuki Sasaki
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Hitomi Hata,
Hitomi Hata
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Kazuyoshi Takeda,
Kazuyoshi Takeda
4Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
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Ko Okumura,
Ko Okumura
4Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
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Luc Van Kaer,
Luc Van Kaer
5Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
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William E. Paul,
William E. Paul
3Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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Kenji Nakanishi
Kenji Nakanishi
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
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Tomohiro Yoshimoto
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Booki Min
3Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Takaaki Sugimoto
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Nobuki Hayashi
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Yuriko Ishikawa
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Yuki Sasaki
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Hitomi Hata
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Kazuyoshi Takeda
4Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Ko Okumura
4Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
Luc Van Kaer
5Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232
William E. Paul
3Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Kenji Nakanishi
1Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
2Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan
Address correspondence to Kenji Nakanishi, Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. Phone: 81-798-45-6572; Fax: 81-798-40-5423; E-mail: [email protected]
*
Abbreviations used in this paper: α-GalCer, α galactosylceramide; CFSE, carboxyfluorescein diacetate succinimidyl ester; L, ligand; MFI, mean fluorescence intensity; Tg, transgenic.
Received:
September 26 2002
Revision Received:
February 14 2003
Accepted:
February 21 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 197 (8): 997–1005.
Article history
Received:
September 26 2002
Revision Received:
February 14 2003
Accepted:
February 21 2003
Citation
Tomohiro Yoshimoto, Booki Min, Takaaki Sugimoto, Nobuki Hayashi, Yuriko Ishikawa, Yuki Sasaki, Hitomi Hata, Kazuyoshi Takeda, Ko Okumura, Luc Van Kaer, William E. Paul, Kenji Nakanishi; Nonredundant Roles for CD1d-restricted Natural Killer T Cells and Conventional CD4+ T Cells in the Induction of Immunoglobulin E Antibodies in Response to Interleukin 18 Treatment of Mice . J Exp Med 21 April 2003; 197 (8): 997–1005. doi: https://doi.org/10.1084/jem.20021701
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