Original article| Volume 124, ISSUE 2, P231-241, August 1994

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

  • W. Ofosu-Appiah
    Brooklyn, New York USA

    From the Division of Immunology, Department of Medicine, Maimonides Medical Center USA

    From the SUNY Health Science Center USA
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  • F. Mokhtarian
    Reprint requests: F. Mokhtrian, PhD, Director, Immunology Research, Maimonides Medical Center, 4802 Tenth Ave., Brooklyn, NY 11219.
    Brooklyn, New York USA

    From the Division of Immunology, Department of Medicine, Maimonides Medical Center USA

    From the SUNY Health Science Center USA
    Search for articles by this author
  • D. Shirazian
    Brooklyn, New York USA

    From the Division of Immunology, Department of Medicine, Maimonides Medical Center USA

    From the SUNY Health Science Center USA
    Search for articles by this author
  • D. Grob
    Brooklyn, New York USA

    From the Division of Immunology, Department of Medicine, Maimonides Medical Center USA

    From the SUNY Health Science Center USA
    Search for articles by this author
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      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 (antl-AChR-α 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-α or pokeweed mltogen. Under these conditions, a high level of antl-AChR-α Ab was produced by cells of patients with MG but not of control subjects. Production of anti-AChR-α 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-α Ab production when added to B cells cocultured with CD4+ T cell clones. Anti-AChR-α 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-α Ab synthesis. Anti-AChR-α 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-α Ab synthesis was inhibited by monocytes. The prostaglandin synthetase inhibitor, indomethacin, partially restored the suppressive effect of monocytes on anti-AChR-α Ab synthesis. These results indicate that induction of anti-AChR-α 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.


      Ab (antibody), AChR-α (alpha chain of acelylcholine receptor), CM (complete medium), HEPES (N-2-hydroxyethylpiperazine-N-2-ethane sulfonic acid), Ig (immunoglobulin), IL-2 (interleukin 2), LDA (limiting dilution analysis), MBP (myelin basic protein), MG (myasthenia gravis), MHC (major histocompatibilily complex), MS (multiple sclerosis), PBL (peripheral blood cells), PBS (phosphate-buffered saline solution), PHA (phytohemagglutinin), PWM (pokeweed mitogen)
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