Extrathymic mechanisms of T cell tolerance: lessons from autoimmune gastritis.
While the thymus plays a key role in the prevention of many autoimmune phenomena it is clear that robust mechanisms external to the thymus are also vital in controlling self-reactive T cells. Here we review the current concepts in the field of extrathymic tolerance and use recent studies of autoimmune gastritis to illustrate how T cells directed to a prominent, clinically relevant autoantigen, namely the gastric proton pump, can be silenced with little or no thymic involvement. Autoimmune gastritis represents one of the most thoroughly characterised autoimmune systems and the knowledge and tools available to study this disease will continue to allow a thorough assessment of the genetic, cellular and molecular events that underlie tolerance and autoimmunity.
Hogan
Thea V
TV
Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Ang
Desmond K Y
DK
Gleeson
Paul A
PA
van Driel
Ian R
IR
D000818:Animals; D015551:Autoimmunity; D005756:Gastritis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism