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Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice

Naturevolume 366pages7275 (1993) | Download Citation

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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

Affiliations

  1. Departments of Microbiology and Immunology

    • Roland Tisch
    • , Xiao-Dong Yang
    • , Steven M. Singer
    • , Roland S. Liblau
    • , Lars Fugger
    •  & Hugh O. McDevitt

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https://doi.org/10.1038/366072a0

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