Model o f Antigen - specific Immunosuppres s ion in Myasthenia Gravis BY STEVE BOGEN , EDNA MOZES , AND SARA FUCHS

Myasthenia gravis is an autoimmune disease characterized by circulating autoantibodies against the acetylcholine receptor (AChR) ~ present on the neuromuscular endplate. It is generally believed that these antibodies are responsible for an accelerated rate of AChR degradation, leading to muscular weakness and fatiguability (1). To date, treatment has involved either the administration of anticholinesterases or nonspecific immunosuppressive measures. Ideally, one would like to specifically eliminate the anti-AChR autoimmune response while not affecting the host's general immune status. Attempts to specifically suppress the anti-AChR immune response by nonmyasthenic derivatives of AChR (2) and by induction of antiidiotype (3) have been reported. Moreover, a recent report indicates that anti-AChR antibody levels in mice can be suppressed if anti-Ia monoclonal antibodies are administered (4). It has been suggested that the underlying defect in myasthenia gravis (as well as other autoimmune diseases) is a deficiency of suppressor T cells (5).Therefore, specific treatment of myasthenia gravis might be achieved if a suitable source of antigen (AChR)-specific suppressor T cells and their secreted factors could be developed. To date, however, no model system has yet been developed demonstrating a means for induction of AChR-specific suppressor T cells. In light of its potential importance to the human disease, we have established the conditions to induce AChR-specific suppressor T cells capable of suppressing the in vitro anti-AChR response. Moreover, we demonstrate that this suppressive effect can be mediated by a secreted factor found in the cell-free supernatant. A key aspect of this work involved the development of an appropriate in vitro anti-AChR assay. The AChR-induced lymphoproliferative assay (6) was found unsuitable for the work described here. Therefore, we applied the assay described by Mishell and Dutton (7) to the AChR antigenic system. This assay is relatively well-characterized in other systems and permits analysis of immunoregulatory T