From T to B and back again: positive feedback in systemic autoimmune disease.
Systemic lupus erythematosus, a prototypical systemic autoimmune disease, is the result of a series of interactions within the immune system that ultimately lead to the loss of self-tolerance to nuclear autoantigens. Here, we present an integrated model that explains how self-tolerance is initially lost and how the loss of tolerance is then amplified and maintained as a chronic autoimmune state. Key to this model are the self-reinforcing interactions of T and B cells, which we suggest lead to perpetuation of autoimmunity as well as its spread to multiple autoantigen targets.
Shlomchik
M J
MJ
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8035, USA.
Craft
J E
JE
Mamula
M J
MJ
D000818:Animals; D001324:Autoantigens; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005075:Biological Evolution; D002450:Cell Communication; D005246:Feedback; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D017634:Self Tolerance; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens