Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies.
Experimental allergic encephalomyelitis (EAE) is a model system for T cell-mediated autoimmune disease. Symptoms of EAE are similar to those of multiple sclerosis (MS) in humans. EAE is induced in susceptible animal strains by immunization with myelin basic protein (MBP) and potent adjuvant. The major T cell response to MBP in B10.PL mice is directed towards an NH2-terminal epitope and involves T cells expressing either V beta 8.2 or V beta 13 gene segments. Animals treated with a TCR V beta 8-specific mAb have a reduced incidence of EAE. We report here that the in vivo administration of a combination of anti-V beta 8.2 and anti-V beta 13 mAbs results in a long-term elimination of T cells involved in the response to MBP. When given before MBP immunization, anti-TCR antibody treatment leads to nearly complete protection against EAE. Antibody treatment also results in a dramatic reversal of paralysis in diseased animals. Thus, treatment with a combination of V beta-specific antibodies is a very effective therapy for the prevention and treatment of EAE. It is hoped that the future characterization of TCR V gene usage in human autoimmune diseases may lead to similar strategies of immune intervention.
Zaller
D M
DM
Division of Biology, California Institute of Technology, Pasadena 91125.
Osman
G
G
Kanagawa
O
O
Hood
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology; D002469:Cell Separation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control* / Q000628:therapy; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010243:Paralysis / Q000534:rehabilitation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D000911:Antibodies, Monoclonal; D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta