title: FK506 prevents induction of rat experimental autoimmune myasthenia gravis.
abstract: Myasthenia gravis (MG) is an organ-specific autoimmune disease attacking nicotinic acetylcholine receptors (AChR) of the neuromuscular junction. Autoantibody production is regulated by autoimmune helper T cells that are specific to AChR. Therefore the suppression of autoimmune T cell activity could reduce myasthenic symptoms. Amongst immunomodulatory therapies aimed at T cells, we studied the therapeutic effect of FK506 as a T cell-specific immunosuppressive agent. Rats in which experimental autoimmune myasthenia gravis (EAMG) was induced by immunization with synthetic peptide of human AChR alpha-subunit residues 125-147 (H alpha 125-147) were treated daily with FK506 (1 mg/kg). FK506 prevented the reduction in amplitude of miniature endplate potential (MEPP) which was induced by H alpha 125-147 immunization. FK506 also suppressed anti-H alpha 125-147 and anti-rat AChR antibody production accompanied by a decrease in the antigen-specific T cell response against H alpha 125-147. These findings indicate that FK506 prevents induction of rat EAMG evoked by immunizing T cells against H alpha 125-147.
authors.affiliation: Department of Neurology, Kanazawa University School of Medicine, Ishikawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: K
authors.initials: K
authors.lastname: Iwasa
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: M
authors.initials: M
authors.lastname: Takamori
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000032:analysis; D002455:Cell Division; D004195:Disease Models, Animal; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011978:Receptors, Nicotinic; D016559:Tacrolimus