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Insulin expression levels in the thymus modulate insulin-specific autoreactive T-cell tolerance: the mechanism by which the IDDM2 locus may predispose to diabetes.
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- Author(s): Chentoufi, Aziz Alami; Polychronakos, Constantin
- Source:
Diabetes; May2002, Vol. 51 Issue 5, p1383-1390, 8p, 2 Charts, 5 Graphs- Subject Terms:
ANIMAL models in research; INSULIN; ANIMAL experimentation; BIOLOGICAL models; COMPARATIVE studies; DISEASE susceptibility; IMMUNOLOGICAL tolerance; TYPE 1 diabetes; ISLANDS of Langerhans; RESEARCH methodology; MEDICAL cooperation; MICE; PROINSULIN; RESEARCH; T cells; THYMUS; EVALUATION research; GENOTYPES - Source:
- Additional Information
- Abstract: Type 1 diabetes results from autoimmune destruction of the insulin-producing pancreatic beta-cells. Evidence from our laboratory and others has suggested that the IDDM2 locus determines diabetes susceptibility by modulating levels of insulin expression in the thymus: the diabetes-protective class III alleles at a repeat polymorphism upstream of the insulin gene are associated with higher levels than the predisposing class I. To directly demonstrate the effect of thymic insulin expression levels on insulin-specific autoreactive T-cell selection, we have established a mouse model in which there is graded thymic insulin deficiency in linear correlation with insulin gene copy numbers, while pancreatic insulin remains unaltered. We showed that mice expressing low thymic insulin levels present detectable peripheral reactivity to insulin, whereas mice with normal levels show no significant response. We conclude that thymic insulin levels play a pivotal role in insulin-specific T-cell self-tolerance, a relation that provides an explanation for the mechanism by which the IDDM2 locus predisposes to or protects from diabetes. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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