Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes
- 19 September 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 5 (10), 1028-1035
- https://doi.org/10.1038/ni1120
Abstract
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.Keywords
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