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The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice

Nature Medicine volume 7, pages 1052–1056 (2001)Cite this article

Abstract

Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells1,2. Vα14–Jα15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d (refs. 3,4). We have previously shown that in vivo activation of Vα14 NKT cells by α-galactosylceramide (α-GalCer) and CD1d potentiates Th2-mediated adaptive immune responses5,6. Here we show that α-GalCer prevents development of diabetes in wild-type but not CD1d-deficient NOD mice. Disease prevention correlated with the ability of α-GalCer to suppress interferon-γ but not interleukin-4 production by NKT cells, to increase serum immunoglobulin E levels, and to promote the generation of islet autoantigen-specific Th2 cells. Because α-GalCer recognition by NKT cells is conserved among mice and humans7,8, these findings indicate that α-GalCer might be useful for therapeutic intervention in human diseases characterized by Th1-mediated pathology such as Type 1 diabetes.

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Figure 1: Analysis of Vα14 NKT cells in NOD mice.
Figure 2: α-GalCer prevents diabetes in NOD mice.
Figure 3: Repeated injection of α-GalCer modulates immune responses in NOD mice.

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Acknowledgements

We thank A.C. Powers for helpful suggestions; M. Nadaf for help with flow cytometry; C. Marlar for critical reading of the manuscript; and A. Herbelin, J.-F. Bach and T. Delovitch for sharing information prior to publication. This work was supported in part by a discovery grant from the Diabetes Research and Training Center at Vanderbilt University (to L.V.K.).

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  1. Seokmann Hong, Michael T. Wilson and Isao Serizawa: S.H., M.T.W. and I.S. contributed equally to this study.

Authors and Affiliations

  1. Department of Microbiology and Immunology, Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Seokmann Hong, Michael T. Wilson, Nagendra Singh, David C. Scherer, Jie Wei & Luc Van Kaer

  2. Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd., Gunma, Japan

    Isao Serizawa, Toru Miura, Tomoku Haba & Yasuhiko Koezuka

  3. Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

    Lan Wu

  4. La Jolla Institute for Allergy and Immunology, San Diego, California, USA

    Olga V. Naidenko & Mitchell Kronenberg

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  1. Seokmann Hong
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Correspondence to Luc Van Kaer.

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Hong, S., Wilson, M., Serizawa, I. et al. The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice. Nat Med 7, 1052–1056 (2001). https://doi.org/10.1038/nm0901-1052

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