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Nature. 1993 Nov 4;366(6450):72-5.

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

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Department of Microbiology and Immunology, Stanford University Medical Center, California 94305.


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 beta-cells. Several beta-cell proteins have been identified as autoantigens, but their importance in the diabetogenic process is not known. The non-obese diabetic (NOD) mouse is a murine model for spontaneous IDDM. Here we determine the temporal sequence of T-cell and antibody responses in NOD mice to a panel of five murine beta-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 beta-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.

[Indexed for MEDLINE]

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