Nature Immunology5, 1028 - 1035 (2004)
Published online: 19 September 2004; | doi:10.1038/ni1120
Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes
Elmar Jaeckel1, Myra A Lipes2
& Harald von Boehmer1
1
Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
2
Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 1 Joslin Place, Boston, Massachusetts 02215, USA.
Although autoimmune diseases can be initiated by immunization with a single antigen, it is not clear whether a single self antigen is essential for the initiation and, perhaps, the perpetuation of spontaneous autoimmunity. Some studies have suggested that insulin may represent an essential autoantigen in type 1 diabetes. Here we show that unlike tolerance to glutamic acid decarboxylase, tolerance to transgenically overexpressed preproinsulin 2 substantially reduced the onset and severity of type 1 diabetes in nonobese diabetic mice. However, some mice still developed type 1 diabetes, suggesting that insulin is a key, but not absolutely essential, autoantigen. The results are consistent with the idea that the human IDDM2 locus controls susceptibility to type 1 diabetes by regulating intrathymic preproinsulin expression.
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