Production of anti-acetylcholine receptor-alpha antibody in vitro by peripheral blood lymphocytes of patients with myasthenia gravis: role of immunoregulatory T cells and monocytes.

To study the role of T cells in T and B cell interaction resulting in production of antibody (Ab) to the alpha chain of acetylcholine receptor (anti-AChR-alpha Ab) in myasthenia gravis (MG), we cocultured peripheral blood-purified B and T cells of patients with MG and of control subjects with and without multiple sclerosis in the presence of AChR-alpha or pokeweed mitogen. Under these conditions, a high level of anti-AChR-alpha Ab was produced by cells of patients with MG but not of control subjects. Production of anti-AChR-alpha Ab by B cells was stimulated by autologous purified or cloned CD4+ T cells, whereas autologous CD8+ T cells had no effect. CD8+ T cells did not suppress anti-AChR-alpha Ab production when added to B cells cocultured with CD4+ T cell clones. Anti-AChR-alpha Ab production was inhibited by monoclonal antibodies against CD4 and class II major histocompatibility complex (MHC) antigens, indicating that these antigens are required for productive T-B cell interactions resulting in anti-AChR-alpha Ab synthesis. Anti-AChR-alpha Ab production by peripheral blood lymphocytes of patients with MG was significantly lower than that by their purified or cloned T cells cultured with B cells. Cell-mixing experiments indicated that anti-AChR-alpha Ab synthesis was inhibited by monocytes. The prostaglandin synthetase inhibitor, indomethacin, partially restored the suppressive effect of monocytes on anti-AChR-alpha Ab synthesis. These results indicate that induction of anti-AChR-alpha Ab production by CD4+ T cell clones requires CD4 and class II MHC antigens and is inhibited by suppressor macrophages and not by CD8+ T cells.