SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE MYASTHENIA-GRAVIS BY NASAL ADMINISTRATION OF ACETYLCHOLINE-RECEPTOR

Experimental autoimmune myasthenia gravis (EAMG) is a well established animal model, which can be induced in various animal species and stra ins with acetylcholine receptor (AChR) and represents an experimental counterpart of human myasthenia gravis (MG). Current immunotherapies o f both EAMG and MG are non-specific and limited by their toxicity. Tol erance to EAMG has been achieved by oral administration of milligram q uantities of Torpedo AChR. In the present report we demonstrate that n asal administration of microgram doses of Torpedo AChR to female Lewis rats prior to immunization with Torpedo AChR and complete Freund's ad juvant resulted in the prevention of subsequently induced EAMG, the su ppression of serum anti-AChR antibody levels, the decrease of delayed- type hypersensitivity responses to AChR, as well as the suppression of AChR-specific immunoglobulin G-secreting cells, AChR-reactive interfe ron-gamma-secreting cells and T cell proliferation in peripheral lymph oid organs, particularly in popliteal and inguinal lymph nodes regiona l to immunization. We conclude that clinical signs of EAMG can be effi ciently prevented by nasal administration of AChR in parallel with the downregulation of both B and T cell responses specific to AChR.