T-cell immunity to acetylcholine receptor and its subunits in Lewis rats over the course of experimental autoimmune myasthenia gravis.
Lymph nodes, spleen and thymus obtained from Lewis rats were examined over the course of experimental autoimmune myasthenia gravis (EAMG) for the distribution and the number of antigen-reactive CD4+ T helper cells which, upon recognition of Torpedo acetylcholine receptor (AChR) or the alpha, beta, gamma or delta subunits of Torpedo AChR, responded by secretion of interferon-gamma (IFN-gamma). T cells with these specificities were detected in these three immune organs. Numbers were highest in lymph nodes. In spleen and thymus, numbers of antigen-reactive T cells did not differ. T cells reacting against the intact AChR were more frequent than T cells recognizing any of the subunits. The immunogenicity between the four subunits did not differ, with the exception that the alpha subunit induced a slightly higher T-cell response. No restriction of the T-cell repertoire to the four subunits was detected during early compared to late phases of EAMG. The AChR and subunit-reactive T cells could--via secretion of effector molecules including IFN-gamma--play an important role in the initiation and perpetuation of EAMG, and consequently also of human myasthenia gravis. T cells with the same specificities were also detected in control animals injected with adjuvant only, but at much lower numbers which were within the range of T cells recognizing the control antigen myelin basic protein. They could represent naturally occurring autoimmune T cells.
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Department of Neurology, Karolinska Institutet, Huddinge Hospital, Stockholm, Sweden.
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D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D003208:Concanavalin A; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000939:Epitopes; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D003208:Concanavalin A; D007371:Interferon-gamma