PRODUCTION OF ANTIACETYLCHOLINE 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 recept or (anti-AChR-alpha Ab) in myasthenia gravis (MG), we cocultured perip heral blood-purified B and T cells of patients with MG and of control subjects with and without multiple sclerosis in the presence of AChR-a lpha 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 co ntrol subjects. Production of anti-AChR-alpha Ab by B cells was stimul ated by autologous purified or cloned CD4(+) T cells, whereas autologo us 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 monoclon al antibodies against CD4 and class II major histocompatibility comple x (MHC) antigens, indicating that these antigens are required for prod uctive T-B cell interactions resulting in anti-AChR-alpha Ab synthesis . Anti-AChR-alpha Ab production by peripheral blood lymphocytes of pat ients with MG was significantly lower than that by their purified or c loned T cells cultured with B cells. Cell-mixing experiments indicated that anti-AChR-alpha Ab synthesis was inhibited by monocytes. The pro staglandin 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 C D4(+) T cell clones requires CD4 and class II MHC antigens and is inhi bited by suppressor macrophages and not by CD8(+) T cells.