Autoaggressive T Lymphocyte in Autoimmune Diseases of the Central Nervous System: Interaction of Autoimmune T Cells with Astroglia

  • H. Wekerle
  • D. Sun
  • R. Meyermann
Part of the NATO ASI Series book series (NSSA, volume 142)


Immunological autoaggression seems to play a much more important role in inflammatory diseases of the nervous system than commonly assumed. As an example chronic viral infection can be associated with T cell mediated reactions against myelin components, as recently demonstrated for measles encephalitis (Johnson et al., 1984). Then, neoplasia of the nervous system is often associated with immune infiltrates, which at least in part may include autoimmune response components (Wilkstrand & Bigner, 1980). Even more important, however, may be the cellular autoimmune responses suspected to dominate the pathogenesis of multiple sclerosis (MS), the main demyelinating disease of the central nervous system (CNS). Although the etiology of MS is completely abscure at present, several different lines of evidence have been put forward supporting an autoimmune pathogenesis of multiple sclerosis (Waksman, 1983). These include the occurrence of oligoclonal immunoglobulin bands in MS cerebrospinal fluid; imbalances in the distribution of T lymphocyte subsets in peripheral blood; abnormal reactivity of natural killer cells; occurrence of myelin-specific lymphocytes, and a genetic linkage disequilibrium between the susceptibility to MS and certain haplotypes of the HLA complex (for review McFarlin & McFarland, 1982). The most convincing argument for the participation of autoimmune reactions in the pathogenesis of MS is, however, the histological appearance of the intracerebral MS lesion. The MS plaque is characterized by three paramount changes: mononuclear infiltrates typically arranged around blood vessels, but also disseminating into the rest of the parenchyme; activation of glial elements, predominantly astrocytes; and destruction of myelin forming elements (Lassmann, 1983).


Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Experimental Allergic Encephalomyelitis Multiple Sclerosis Plaque Central Nervous System Parenchyme 


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  1. Ben-Nun, A., Wekerle, H., and Cohen, I. R., 1981, The rapid isolation of clonable, antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis, Eur. J. Immunol., 11: 195–199.CrossRefGoogle Scholar
  2. Ben-Nun, A. and Cohen, I. R., 1982, Experimental autoimmune encephalomyelitis (EAE) mediated by T cell lines: Process of selection of lines and characterization of the cells, J. Immunol., 129: 303–308.Google Scholar
  3. Brosnan, C. F., Bornstein, M. B., and Bloom, B. R., 1981, The effects of macrophages depletion on the clinical and pathological expression of experimental allergic encephalomyelitis, J. Immunol., 126: 614–620.Google Scholar
  4. Cammer, W., Bloom, B. R., Norton, W. T., and Gordon, S., 1978, Degradation of basic protein in myelin by neural proteases secreted by stimulated macrophages: A possible mechanism of inflammatory demyelination, Proc. Nat. Acad. Sci., 75: 1554–1558.CrossRefGoogle Scholar
  5. Cantrell, D. A. and Smith, K. A., 1983, Transient expression of interleukin 2 receptors. Consequenced for T cell growth, J. Exp. Med., 158: 1895–1911.CrossRefGoogle Scholar
  6. Eng, L. F., 1985, Glial fibrillary acidic protein (GFAP): The major protein of glial intermediate filaments in differentiated astrocytes, J. Neuroimmunol., 8: 203–213.CrossRefGoogle Scholar
  7. Fierz, W., Endler, B., Reske, K., Wekerle, H., and Fontana, A., 1985, Astrocytes as antigen presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation, J. Immunol., 134: 3785–3793.Google Scholar
  8. Fontana, A., Fierz, W., and Wekerle, H., 1984, Astrocytes present myelin basic protein to encephalitogenic T cell lines, Nature, 307: 273–275.CrossRefGoogle Scholar
  9. Hirsch, M. A., Wietzerbin, J., Pierres, M., and Goridis, C., 1983, Expression of Ia antigens by cultured astrocytes treated with gamma-interferon, Neurosci. Lett., 41: 199–204.CrossRefGoogle Scholar
  10. Johnson, R. T., Griffin, D. E., Hirsch, R. L., Wolinsky, J. S., Rodenbeck, S., de Soriano, I. L., and Vaisberg, A., 1984, Measles encephalomyelitis. Clinical and immunological studies, N. Engl. J. Med., 310: 137–141.CrossRefGoogle Scholar
  11. Kibler, R. F., Fritz, R. B., Chou, F. C.-H., Jean Chou, C.-H., Peacocke, N. Y., Brown, N. M., and McFarlin, D. F., 1977, Immune response of Lewis rats to peptide 01 (residues 68–88) of guinea pig and rat myelin basic protein, J. Exp. Med., 146: 1323–1331.CrossRefGoogle Scholar
  12. Kung, P. C., Goldstein, G., Reinherz, E. L., and Schlossman, S. F., 1979, Monoclonal antibodies defining distinctive human T cell surface antigens, Science, 206: 347–349.CrossRefGoogle Scholar
  13. Lassman, H., 1983, Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis, Springer Verl., Berlin.CrossRefGoogle Scholar
  14. Mason, D. W., Arthur, R. P., Dallman, M. J., Green, J. R., Spickett, G. P., and Thomas, M. L., 1983, Functions of rat T lymphocyte subsets isolated by means of monoclonal antibodies, Immunol. Rev., 74: 57–82.CrossRefGoogle Scholar
  15. McFarlin, D. E. and McFarland, H. F., 1982, Multiple Sclerosis, N. Engl. J. Med., 307: 1183–1188 and 307:1246-1251.CrossRefGoogle Scholar
  16. Omlin, F. X., Webster, H.deF., Palkovits, C.G., and Cohen, S. R., 1982, Immunocytochemical localization of basic protein in major dense line regions of central and peripheral myelin, J. Cell Biol., 95: 242–248.CrossRefGoogle Scholar
  17. Paterson, P. Y., 1982, Molecular and cellular determinants of neuroimmunological inflammatory disease, Fed. Proc., 41: 2569–2576.Google Scholar
  18. Raine, C. S. and Traugott, U., 1982, The pathogenesis and therapy of multiple sclerosis is based upon the requirement of a combination of myelin antigen for autoimmune demyelination, J. Neuroimmunol., 2: 83–91.CrossRefGoogle Scholar
  19. Schluesener, H. J. and Wekerle, H., 1985, Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: In vitro selection from unprimed rat T lymphocyte population, J. Immunol., 135: 3128–3133.Google Scholar
  20. Sriram, S., Solomon, D., Rouse, R. V., and Steinman, L., 1982, Identification of T cell subset and B lymphocytes in mouse brain experimental allergic encephalomyelitis lesions, J. Immunol., 129: 1649–1651.Google Scholar
  21. Sun, D. and Wekerle, H., 1986, Ia-restricted encephalitogenic T lymphocyte mediating EAE lyse autoantigen-presenting astrocytes, Nature, 320: 70–72.CrossRefGoogle Scholar
  22. Swanborg, R. H., 1983, Autoimmune effector cells. V. A monoclonal antibody specific for rat T helper cells inhibits adoptive transfer of autoimmune encephalomyelitis, J. Immunol., 130: 1503–1505.Google Scholar
  23. Wass, K., Lassmann, H., Wekerle, H., and Wisniewski, H. M., 1986, The distribution of Ia antigens in the lesions of rat acute experimental allergic encephalomyelitis, A. Neuropathol., 70: 149–160.CrossRefGoogle Scholar
  24. Waksman, B. H., 1983, Immunity and the nervous system: Basic Tenets, Ann. Neurol., 13: 578–591.CrossRefGoogle Scholar
  25. Wekerle, H., 1984, The lesion of acute experimental autoimmune encephalomyelitis: Isolation and membrane phenotypes of lympho-vascular complexes from encephalitic rat brain white matter, Lab. Invest., 51: 199–205.Google Scholar
  26. Wekerle, H. and Fierz, W., 1985, T cell approach to demyelinating diseases, Springer Semin. Immunopathol., 8: 97–110.Google Scholar
  27. Wekerle, H., Linington, C., Lassmann, H., and Meyermann, R., 1986, Cellular immune reactivity within the CNS, TINS, 9: 271–277.Google Scholar
  28. Wilkstrand, C. J. and Bigner, D. D., 1980, Immunobiologic aspects of the brain and human gliomas, Am. J. Pathol., 98: 516–658.Google Scholar
  29. Wisniewski, H. M., 1978, Immunopathology of demyelination in autoimmune diseases and virus infection, Br. Med. Bull., 33: 54–59.Google Scholar
  30. Wong, G. H. W., Bartlett, P. F., Clark-Lewis, I., McKimm-Breschkin, J. L., and Schrader, J. W., 1985, Interferon-γ induces the expression of H-2 and Ia antigens on brain cells, J. Neuroimmunol., 7: 255–278.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • H. Wekerle
    • 1
  • D. Sun
    • 1
  • R. Meyermann
    • 1
  1. 1.Clincal Research Unit for Multiple SclerosisMax-Planck-InstituteWürzburgGermany

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