Recessive tolerance to preproinsulin 2 reduces but does not abolish type 1 diabetes.
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.
Jaeckel
Elmar
E
Harvard Medical School, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.
Lipes
Myra A
MA
von Boehmer
Harald
H
D000595:Amino Acid Sequence; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D007328:Insulin; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
D007328:Insulin; D011498:Protein Precursors; D015375:Receptors, Interleukin-2; C013737:preproinsulin; D011384:Proinsulin