FK506 PREVENTS INDUCTION OF RAT EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS

Myasthenia gravis (MG) is an organ-specific autoimmune disease attacki ng nicotinic acetylcholine receptors (AChR) of the neuromuscular junct ion. 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 immunomodulato ry therapies aimed at T cells, we studied the therapeutic effect of FK 506 as a T cell-specific immunosuppressive agent. Rats in which experi mental 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 preven ted the reduction in amplitude of miniature endplate potential (MEPP) which was induced by H alpha 125-147 immunization. FK506 also suppress ed anti-H alpha 125-147 and anti-rat AChR antibody production accompan ied by a decrease in the antigen-specific T cell response against H al pha 125-147. These findings indicate that FK506 prevents induction of rat EAMG evoked by immunizing T cells against H alpha 125-147. (C) 199 7 Academic Press Limited.