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Genetic lesions in T‐cell tolerance and thresholds for autoimmunity
Author(s) -
Liston Adrian,
Lesage Sylvie,
Gray Daniel H. D.,
Boyd Richard L.,
Goodnow Christopher C.
Publication year - 2005
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.0105-2896.2005.00253.x
Subject(s) - autoimmunity , biology , immunology , immune tolerance , self tolerance , genetics , immune system
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.