Genetic lesions in T-cell tolerance and thresholds for autoimmunity.
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.
Liston
Adrian
A
John Curtin School of Medical Research and The Australian Phenomics Facility, The Australian National University, Canberra, ACT 2601, Australia.
Lesage
Sylvie
S
Gray
Daniel H D
DH
Boyd
Richard L
RL
Goodnow
Christopher C
CC
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics* / Q000276:immunology*; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D001324:Autoantigens