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Genetic lesions in T-cell tolerance and thresholds for autoimmunity


* Christoper C. Goodnow
Division of Immunology and Genetics
The John Curtin School of Medical Research
P.O. Box 334, Mills Road
Canberra, ACT 2601
Tel.: +61 2 6125 3621
Fax: +61 2 6125 8512


Summary:  The cause of common organ-specific autoimmune diseases is poorly understood because of genetic and cellular complexity in humans and animals. Recent advances in the understanding of the mechanisms of the defects underlying autoimmune disease in autoimmune polyendocrinopathy syndrome type 1 and non-obese diabetic mice suggest that failures in central tolerance play a key role in predisposition towards organ-specific autoimmunity. The lessons from such rare monogenic autoimmune disorders and well-characterized polygenic traits demonstrate how subtle quantitative trait loci can result in large changes in the susceptibility to autoimmunity. These data allow us to propose a model relating efficiency of thymic deletion to T-cell tolerance and susceptibility to autoimmunity.