Induction of acetylcholine receptor-specific suppression. An in vitro model of antigen-specific immunosuppression in myasthenia gravis.
This report describes the in vivo and in vitro induction of murine (AChR)-specific suppressor T cells (Ts) and T cell factors (TsF), and the development of an appropriate assay system for their measurement. The assay described is based on the in vitro Mishell-Dutton culture system. Using this assay, it was shown that the AChR-specific helper cell is an Lyt-2- radiosensitive T cell. Moreover, the proliferating cell measured in the lymphocyte transformation assay was shown to provide AChR-specific T cell help. In vivo induction of Ts cells is achieved by injection of soluble AChR; potent AChR-specific suppression is found in the spleen 1 wk later. In vitro induction of Ts cells involves the primary education of naive splenocytes by culturing them with high concentrations of AChR. Both the in vivo- and in vitro-induced Ts cells were shown to secrete AChR-specific factors that mediate their suppressive effects. The possibility of specifically suppressing the AChR-immune response may be of a particular clinical importance since the AChR is the target autoantigen in the neuromuscular autoimmune disease myasthenia gravis.
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009157:Myasthenia Gravis / Q000276:immunology*; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology*; D013491:Suppressor Factors, Immunologic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000950:Antigens, Ly; D000939:Epitopes; D008222:Lymphokines; D011950:Receptors, Cholinergic; D013491:Suppressor Factors, Immunologic