FK506 prevents induction of rat experimental autoimmune myasthenia gravis

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.