Advertisement

Permanent Lines of T Lymphocytes Specific for Acetylcholine Receptors: A Clonal Approach to Study the Pathogenesis of Myasthenia Gravis

  • B. C. G. Schalke
  • R. Hohlfeld
  • I. Kalies
  • A. Ben-Nun
  • I. R. Cohen
  • H. Wekerle

Abstract

Myasthenia gravis is a disease of the neuromuscular synapse. Studies during the past decade have unequivocally established that the pathogenic defect in myasthenia is due to autoantibodies specific for the nicotinic acetylcholine receptors (AChR) of the end plate. These autoantibodies were demonstrated to bind to receptor bearing areas (1), they can transfer disease to formerly normal recipient animals (2), and cause accelerated receptor decay on the postsynaptic membranes (3). Humoral antibodies reflect, however, only one aspect of the autoimmune pathogenesis of myasthenia gravis. 1) There is strong evidence that, in addition, autoimmune T lymphocytes are critically involved in the pathogenesis of myasthenia gravis. This is most probably true in the afferent stages of the disease mechanism, and possibly also in the effector phase. The evidence for T cell participation in myasthenia gravis seems to be (loosely) linked to certain determinants of the human major histocompatibility gene complex, HLA (4). It is known that the immune response genes coded for within the major histocompatibility complex predominantly act in T cell dependent stages of the immune response (5). 2) Some, but possibly not all patients with myasthenia gravis possess peripheral blood lymphocytes reactive against isolated acetylcholine receptors by proliferation (6) or by secretion of lymphokines (7).

Keywords

Acetylcholine Receptor Cell Subline Mixed Leukocyte Culture Idiotypic Interaction Experimental Autoimmune Myasthenia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Engel, A.G., Lambert, E.H. and Howard F.H., Mayo Clin. Proc. 52: 267–280 (1977).PubMedGoogle Scholar
  2. 2.
    Toyka, K.V., Drachman, D.B., Pestronk, A. and Kao, I., Science 190: 397–399 (1975).PubMedCrossRefGoogle Scholar
  3. 3.
    Appel, S.H., Anwyl, R., Mc Adams, M.W. and Elias, S., Proc. Nat. Sci. 74: 2130–2134 (1977).CrossRefGoogle Scholar
  4. 4.
    Feltkamp, T.E.W., Van Den Berg-Loonen, P.M., Nijenhuis, L.E., Engelfriet, C.P., Van Rossum, A.L., Van Loghem, J.J. and Osterhuis, H.J.G.H., Br. Med. J. i: 131–133 (1974).Google Scholar
  5. 5.
    McDevitt, H.O., N. Ens. J. Med. 303: 1514–1517 (1980).CrossRefGoogle Scholar
  6. 6.
    Conti-Tronconi, B.M., Morgutti, B.M., Sgirlanzoni, A. and Clementi, F., Neurol. 29: 496–501 (1979).Google Scholar
  7. 7.
    Abramsky, O., Aharonov, A., Webb, C. and Fuchs, S., Clin. Exp. Immunol. 19: 11–16 (1975).PubMedGoogle Scholar
  8. 8.
    Lefvert, A.K., Bergström, K., Scand. J. Immunol. 813: 115–119 (1978).Google Scholar
  9. 9.
    Cantor, H., Boyse, E.A., Cold Spring Harbor Symp. Quant Biol. 41: 23–32 (1977).PubMedCrossRefGoogle Scholar
  10. 10.
    Wekerle, H.R., Hohlfeld, U.P., Ketelson, J.R., Ketelson, J.R., Kalies, I., Ann. N. Y. Acad. Sci. 377: 455–476 (1981).PubMedCrossRefGoogle Scholar
  11. 11.
    Wekerle, H., J. Exp. Med. 147: 233–250 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    Wekerle, H. and Begemann, M., J. Immunol. 116: 159–164 (1976).PubMedGoogle Scholar
  13. 13.
    Wekerle, H., Ben-Nun, A., Hurtenbach, U. and Prester, M., in: “Genetic Control of Autoimmunity”, Rose, N.R., Warner, N.L. and Bigazzi, P. (Eds.), Academic Press, New York, pp. 413–432 (1978).Google Scholar
  14. 14.
    Hohlfeld, R., Kalies, I., Heinz, F., Kalden, J.R. and Wekerle, H, J. Immunol. 126: 1355–1359 (1981)PubMedGoogle Scholar
  15. 15.
    Hohlfeld, R., Kalies, I., Ernst, M., Ketelson, U.P. and Wekerle, H., J. Neurol. Sci. (in press).Google Scholar
  16. 16.
    Ben-Nun, A., Wekerle, H. and Cohen, I.R., Eur. J. Immunol. 11: 195–199 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • B. C. G. Schalke
    • 1
  • R. Hohlfeld
    • 1
  • I. Kalies
    • 1
  • A. Ben-Nun
    • 2
  • I. R. Cohen
    • 2
  • H. Wekerle
    • 1
  1. 1.Clinical Research Unit for Multiple SclerosisMax-Planck-SocietyWürzburgGermany
  2. 2.Department of Cell BiologyWeizmann InstituteRehovotIsrael

Personalised recommendations