Immunotherapy for myasthenia gravis: a murine model.
In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
P
P
Christadoss
M J
MJ
Dauphinee
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D004195:Disease Models, Animal; D000939:Epitopes; D005260:Female; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D009157:Myasthenia Gravis / Q000276:immunology / Q000628:therapy*; D011950:Receptors, Cholinergic / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D001323:Autoantibodies; D000939:Epitopes; D011950:Receptors, Cholinergic