Immunoregulation in experimental autoimmune myasthenia gravis--about T cells, antibodies, and endplates.
Experimental autoimmune myasthenia gravis (EAMG) can be induced in a large number of animal species by active immunization (AI) AChR, by passive transfer (PT) of anti-AChR antibodies, by autologous bone marrow transplantation and cyclosporin (BMT-Cy), or spontaneously. Depending on the model used, different immunological mechanisms are operational. In the AI model, the T cell is pivotal in directing the anti-AChR antibody production towards pathogenic, that is, cross-linking and complement-fixing antibodies. Injection of anti-AChR antibodies alone suffices to induce EAMG, excluding the role of specific cell-mediated immune responses in the effector phase of the disease. Aged animals are resistant to the induction of AI and PT EAMG. This resistance is localized at the postsynaptic membrane containing more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals. In BMT-CyA EAMG, a dysregulation of the immune system in the absence of immunization is capable of inducing myasthenia. The role of these animal models in relation to pathogenesis and immunotherapy is discussed.
Department of Neurology, Research Institute of Brain and Behavior, University of Maastricht, 6229 ER Maastricht, The Netherlands. mdba@sneu.azm.nl
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M
De Baets
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M
Stassen
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M
Losen
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Zhang
B
B
Machiels
D000818:Animals; D000906:Antibodies / Q000276:immunology; D016026:Bone Marrow Transplantation; D018958:CD55 Antigens / Q000276:immunology; D018957:CD59 Antigens / Q000276:immunology; D002417:Cattle; D015316:Genetic Therapy; D006168:Guinea Pigs; D007114:Immunization; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009045:Motor Endplate / Q000276:immunology* / Q000503:physiopathology; D009124:Muscle Proteins / Q000235:genetics; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000378:metabolism / Q000637:transplantation; D019096:Vitronectin
D000906:Antibodies; D018958:CD55 Antigens; D018957:CD59 Antigens; D009124:Muscle Proteins; D011950:Receptors, Cholinergic; D019096:Vitronectin; C051609:peripheral membrane protein 43K