Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice (original) (raw)

Nature volume 366, pages 72–75 (1993)Cite this article

Abstract

KNOWING the autoantigen target(s) in an organ-specific autoimmune disease is essential to understanding its pathogenesis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease characterized by lymphocytic infiltration of the islets of Langerhans (insulitis) and destruction of insulin-secreting pancreatic β-cells1. Several β-cell proteins have been identified as autoantigens, but their importance in the diabetogenic process is not known2. The non-obese diabetic (NOD) mouse is a murine model for spontaneous IDDM3. Here we determine the temporal sequence of T-cell and antibody responses in NOD mice to a panel of five murine β-cell antigens and find that antibody and T-cell responses specific for the two isoforms of glutamic acid decarboxylase (GAD) are first detected in 4-week-old NOD mice. This GAD-specific reactivity coincides with the earliest detectable response to an islet extract, and with the onset of insulitis. Furthermore, NOD mice receiving intrathymic injections of GAD65 exhibit markedly reduced T-cell proliferative responses to GAD and to the rest of the panel, in addition to remaining free of diabetes. These results indicate that the spontaneous response to β-cell antigens arises very early in life and that the anti-GAD immune response has a critical role in the disease process during this period.

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Author notes

  1. Hugh O. McDevitt: Medicine, Stanford University Medical Center, Stanford, California 94305, USA

Authors and Affiliations

  1. Departments of Microbiology and Immunology,
    Roland Tisch, Xiao-Dong Yang, Steven M. Singer, Roland S. Liblau, Lars Fugger & Hugh O. McDevitt

Authors

  1. Roland Tisch
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  2. Xiao-Dong Yang
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  3. Steven M. Singer
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  4. Roland S. Liblau
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  5. Lars Fugger
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  6. Hugh O. McDevitt
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Tisch, R., Yang, XD., Singer, S. et al. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice.Nature 366, 72–75 (1993). https://doi.org/10.1038/366072a0

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