Current therapy of patients with myasthenia gravis (MG) commonly involves general immunosuppressive treatment. Though effective in most cases, this treatment has significant drawbacks. Ideally, treatment of MG should eliminate only the autoimmune response against acetylcholine receptor (AChR), without otherwise altering the immune system. The goal of this project is to devise an immunotherapeutic strategy based on specific suppression of the antibody response to AChR by suppressor cells. These studies will initially be carried out in rats with experimental autoimmune myasthenia gravis (EAMG); as the methods are developed, we will apply them to lymphocytes from patients with MG. Our approach will be as follows: 1. To induce T-suppressor cells specific for AChR (Ts-AChR) by two different methods: 1) exposure of lymphocytes to the immunosuppressive drug, cyclosporin A in conjunction with AChR, and 2) exposure of lymphocytes to AChR-coupled syngeneic cells to induce a suppressor cell cascade. These procedures have the advantage of inducing Ts-AChR in a population of lymphocytes already sensitized to AChR without triggering an autoimmune response. 2. To enrich suppressor cells by standard cell selection techinques and expand the population of Ts-AChR in cultures supplemented with T cell growth factor (Interleukin 2). 3. To transfer the expanded population of Ts-AChR back to animals with experimental MG in order to suppress the autoimmune response to AChR. It is anticipated that this work will lead to the development of a strategy for the specific immunotherapy of EAMG. The ultimate goal is to apply similar methods in the treatment of human patients with MG.
