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Abstract
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.
Abbreviations:
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)To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
February 9,
1994
Received in revised form:
January 25,
1994
Received:
June 22,
1993
Footnotes
☆Supported by Grants R29NS24688 from the National Institutes of Health, RG 1004-A-1 from the National Multiple Sclerosis Society, and a grant from the Maimonides Research and Development Foundation.
Identification
Copyright
© 1994 Published by Elsevier Inc.
