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Are current immunological concepts of multiple sclerosis reflected by the immunopathology of its lesions?

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Abstract

Immunopathological studies on multiple sclerosis (MS) brain clearly indicate that a T cell-mediated immune response is the driving force in the induction of the lesions. This T cell-mediated response alone, however, is not sufficient to explain the widespread and selective destruction of myelin sheaths. According to present evidence, it is likely that antibodies directed against surface components of myelin sheaths are at least one factor involved in the demyelinating process. The patterns of inflammation, demyelination and oligodendrocyte destruction, however, suggest that the pathogenesis of the lesions may be fundamentally different in individual MS patients and that autoimmunity may not be the sole cause. In the case of autoimmune reactions various different proteins of the nervous system may become targets and it appears unlikely, that myelin basic protein is a major candidate for a pathogenetic role in MS.

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References

  1. Brück W, Schmied M, Suchanek G, Brück Y, Breitschopf H, Poser S, Piddlesden S, Lassmann H (1994) Oligodendrocytes in the early course of MS. Ann Neurol 35:65.

    Google Scholar 

  2. Butt AM, Jenkins HG (1994) Morphological changes in oligodendrocytes in the intact mouse optic nerve following intravitreal injection of tumor necrosis factor. J Neuroimmunol 51:27.

    Google Scholar 

  3. Charcot JM (1868) Histologie de la sclerose en plaque. Gaz Hopital (Paris) 41:554.

    Google Scholar 

  4. Compston DA, Morgan BP, Campbell AK, Wilkinsw P, Cole G, Thomas ND, Jasani B (1989) Immunocytochemical localization of the terminal complement complex in MS. Neuropathol Appl Neurobiol 15:307.

    Google Scholar 

  5. Cross AH, O'Mara T, Raine CS (1993) Chronologic localization of myelin reactive cells in the lesions of relapsing EAE: implications for the study of MS. Neurology 43:1028.

    Google Scholar 

  6. Dawson JW (1916) The histology of disseminated sclerosis. Trans R Soc Lond 50:517.

    Google Scholar 

  7. Dore-Duffy P, Washington R, Dragovic L (1993) Expression of endothelial cell activation antigens in microvessels from patients with multiple sclerosis. Adv Exp Med Biol 331:243.

    Google Scholar 

  8. Esiri MM (1980) Multiple sclerosis: a quantitative and qualitative study on immunoglobulin-containing cells in the central nervous system. Neuropath Appl Neurobiol 6:9.

    Google Scholar 

  9. Estes ML, Rudick RA, Barnett GH, Ransohoff RM (1990) Stereotactic biopsy of an active multiple sclerosis lesion. Immunocytochemical analysis and neuropathologic correlation with magnetic resonance imaging. Arch Neurol 47:1299.

    Google Scholar 

  10. Freedman MS, Ruijs TC, Selin LK, Antel JP (1991) Peripheral blood γ δ T cells lyse fresh human brain derived oligodendrocytes. Ann Neurol 30:794.

    Google Scholar 

  11. Gerritse K, Deen C, Fasbender M, Ravid R, Boersma W, Claassen E (1994) The involvement of specific anti myelin basic protein antibody forming cells in multiple sclerosis immunopathology. J Neuroimmunol 49:153.

    Google Scholar 

  12. Hayashi T, Morimoto C, Burks JS, Kerr C, Hauser SL (1988) Dual label immunocytochemistry of the active multiple sclerosis lesion: major histocompatibility complex and activation antigens. Ann Neurol 24:523.

    Google Scholar 

  13. Hofman FM, von Hahnwehr RI, Dinarello CA, Mizel SB, Hinton D, Merrill JE (1986) Immunoregulatory molecules and IL2 receptors identified in multiple sclerosis lesions. J Immunol 136:3239.

    Google Scholar 

  14. Iwasaki Y, Sako K, Tsunoda I, Ohara Y (1993) Phenotypes of mononuclear cell infiltrates in human central nervous system. Acta Neuropathol 85:653.

    Google Scholar 

  15. Jellinger K (1969) Einige morphologische Aspekte der multiplen Sklerose. Wien Z Nervenheilk [Suppl] II:12.

    Google Scholar 

  16. Kerlero de Rosbo N, Milo R, Lees MB, Burger D, Bernard CC, Ben-Nun A (1994) Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendroglia glycoprotein. J Clin Invest 92:2602.

    Google Scholar 

  17. Kojima K, Berger T, Lassmann H, Hinze-Selch D, Zhang Y, Germann J, Reske K, Wekerle H, Linington C (1994) Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100β molecule, a calcium binding protein of astroglia. J Exp Med 118:817.

    Google Scholar 

  18. Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Springer, Berlin Heidelberg New York Tokyo.

    Google Scholar 

  19. Lassmann H, Kitz K, Wisniewski HM (1981) In vivo effect of sera from animals with chronic relapsing experimental allergic encephalomyelitis on central and peripheral myelin. Acta Neuropathol (Berl) 55:297.

    Google Scholar 

  20. Lassmann H, Brunner C, Bradl M, Linington C (1988) Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol (Berl) 75:566.

    Google Scholar 

  21. Lassmann H, Zimprich F, Rössler K, Vass K (1991) Inflammation in the nervous system. Basic mechanisms and immunological concepts. Rev Neurol (Paris) 147:763.

    Google Scholar 

  22. Lassmann H, Suchanek G, Ozawa K (1994) Histopathology and the blood-cerebrospinal fluid barrier in multiple sclerosis. Ann Neurol [Suppl] 36:S42.

    Google Scholar 

  23. Li H, Newcombe J, Groome NP, Cuzner ML (1993) Characterization and distribution of phagocytic macrophages in multiple sclerosis plaques. Neuropathol Appl Neurobiol 19:214.

    Google Scholar 

  24. Linington C, Lassmann H (1987) Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligo-dendroglia glycoprotein (MOG). J Neuroimmunol 17:61.

    Google Scholar 

  25. Linington C, Bradl M, Lassmann H, Brunner Ch, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies against myelin/oligodendroglia glycoprotein. Am J Pathol 130:135.

    Google Scholar 

  26. Linington C, Berger T, Perry L, Weerth S, Hinze-Selch D, Lu H, Lassmann H, Wekerle H (1993) T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system. Eur J Immunol 23:1364.

    Google Scholar 

  27. Louis JC, Magal E, Takayama S, Varon S (1993) CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 259:689.

    Google Scholar 

  28. Lumsden CE (1970) The neuropathology of multiple sclerosis. Handb Clin Neurol 9:217.

    Google Scholar 

  29. Marburg O (1906) Die sogenannte “akute Multiple Sklerose”. Jahrb Psychiatr 27:211.

    Google Scholar 

  30. Matthews WB (1991) Clinical aspects. In: Matthews WB, Compston A, Allen I, Martyn CN (eds) McAlpine's multiple sclerosis. Churchill Livingstone, Edinburgh, 107–138.

    Google Scholar 

  31. Merrill JE (1992) Proinflammatory and antiinflammatory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome. J Immunother 12:167.

    Google Scholar 

  32. Mussini JM, Hauw JJ, Escourolle R (1977) Immunofluorescence studies of intracytoplasmic immunoglobulin binding lymphoid cells (CICL) in the central nervous system. Report of 32 cases including 19 MS. Acta Neuropathol (Berl) 40:227.

    Google Scholar 

  33. Oksenberg JR, Panzara MA, Begovich AB, Mitchell D, Erlich HA, Murray RS, Shimonkevitz R, Sherritt M, Rothbard J, Bernard CC (1993) Selection for T cell receptor Vβ-Dβ-Jβ gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature 362:68.

    Google Scholar 

  34. Olsson T (1992) Immunology of MS. Curr Opin Neurol Neurosurg 5:195.

    Google Scholar 

  35. Ozawa K, Suchanek G, Breitschopf H, Brück W, Budka H, Jellinger K, Lassmann H (1994) Patterns of oligodendroglia pathology in multiple sclerosis. Brain 117:1311.

    Google Scholar 

  36. Prineas JW (1985) The neuropathology of multiple sclerosis. Handb Clin Neurol 47:213.

    Google Scholar 

  37. Prineas JW, Raine CS (1976) Electron microscopy and immunoperoxidase studies in early multiple sclerosis lesions. Neurology 26:29.

    Google Scholar 

  38. Prineas JW, Kwoon EE, Goldenberg PZ, Ilyas AA, Quarles RH, Benjamins JA, Sprinkle TJ (1989) MS. Oligodendrocyte proliferation and differentiation in fresh lesions. Lab Invest 61:489.

    CAS  PubMed  Google Scholar 

  39. Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137.

    Google Scholar 

  40. Prineas JW, Barnard RO, Revesz T, Kwon EE, Sharer L, Cho ES (1993) Multiple sclerosis. Pathology of recurrent lesions. Brain 116:681.

    Google Scholar 

  41. Raine CS, Scheinberg L, Waltz JM (1981) Multiple sclerosis: oligodendroglia survival and proliferation in an active established lesion. Lab Invest 45:534.

    CAS  PubMed  Google Scholar 

  42. Rodriguez M, Scheithauer BW, Forbes G, Kelly PJ (1993) Oligodendrocyte injury is an early event in lesions of multiple sclerosis. Mayo Clin Proc 68:627.

    Google Scholar 

  43. Schlüsener HJ, Meyermann R (1993) Intercrines in brain pathology. Expression of intercrines in a multiple sclerosis and Morbus Creutzfeldt-Jakob lesion. Acta Neuropathol 86:393.

    Google Scholar 

  44. Scolding N, Linington C, Compston A (1989) Immune mechanisms in the pathogenesis of demyelinating diseases. Autoimmunity 4:131.

    Google Scholar 

  45. Scolding NJ, Jones J, Compston DA, Morgan BP (1990) Oligodendrocyte susceptibility to injury by T cell perform. Immunology 70:6.

    Google Scholar 

  46. Seitelberger F (1960) Histochemistry of demyelinating diseases proper including allergic encephalomyelitis and Pelizaeus-Merzbacher's disease. In: Cummings JN (ed) Modern scientific aspects of neurology. Arnold, London, pp 146.

    Google Scholar 

  47. Seitelberger F, Jellinger K, Tschabitscher H (1958) Zur Genese der akuten Entmarkungsenzephalitis. Wien Klin Wochenschr 70:453.

    Google Scholar 

  48. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339.

    Google Scholar 

  49. Selmaj K, Brosnan CF, Raine CS (1991) Colocalization of lymphocytes bearing γ δ T cell receptor and heat-shock protein hsp65+ oligodendrocytes in multiple sclerosis. Proc Natl Acad Sci USA 88:6452.

    Google Scholar 

  50. Selmaj K, Raine CS, Cannella B, Brosnan CF (1991) Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. J Clin Invest 87:949.

    Google Scholar 

  51. Skundric DS, Kim C, Tse HY, Raine CS (1993) Homing of T cells to the central nervous system throughout the course of relapsing experimental autoimmune encephalomyelitis in Thy-1 congenic mice. J Neuroimmunol 46:113.

    Google Scholar 

  52. Sobel RA, Mitchell ME (1989) Fibronectin in multiple sclerosis lesions. Am J Pathol 135:161.

    Google Scholar 

  53. Sobel RA, Hafler DA, Castro EE, Morimoto C, Weiner HL (1988) The 2H4 (CD45R) antigen is selectively decreased in multiple sclerosis lesions. J Immunol 140:2210.

    Google Scholar 

  54. Sobel RA, Mitchell ME, Fondren G (1990) Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136:1309.

    Google Scholar 

  55. Traugott U (1987) Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol 16:283.

    Google Scholar 

  56. Traugott U, Lebon P (1988) Multiple sclerosis: involvement of interferons in lesion pathogenesis. Ann Neurol 24:243.

    Google Scholar 

  57. Uchimura I, Shiraki H (1957) A contribution to the classification and the pathogenesis of demyelinating encephalomyelitis. J Neuropathol Exp Neurol 16:139.

    Google Scholar 

  58. Waksman BH, Porter H, Lees MB, Adams RD (1954) A study of the chemical nature and components of bovine white matter effective in producing allergic encephalomyelitis in the rabbit. J Exp Med 100:451.

    Google Scholar 

  59. Weerth S, Berger T, Lassmann H, Wekerle H, Linington C (1994) Analysis of the autoimmune response to myelin-associated glycoprotein (MAG) in the Lewis rat. Abstracts of the First Eur Meeting on Glia Cell Function, Unversity of Heidelberg, Heidelberg 24–27 March 1994, p 184.

    Google Scholar 

  60. Weiner HL, Mackin GA, Matsui M, Orav EJ, Khoury SJ, Dawson DM, Hafler DA (1993) Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science 259:1321.

    Google Scholar 

  61. Weinshenker BG, Ebers GC (1987) The natural history of multiple sclerosis. Can J Neurol Sci 14:255.

    Google Scholar 

  62. Woodroofe MN, Cuzner ML (1993) Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. Cytokine 5:583.

    Google Scholar 

  63. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA (1992) γ δ T cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci USA 89:4588.

    Google Scholar 

  64. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA (1992) T cell receptor V α-V β repretoire and cytokine gene expression in active multiple sclerosis lesions. J Exp Med 175:993.

    Google Scholar 

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Authors and Affiliations

  1. Neurological Institute, University of Vienna, Schwarzspanierstrasse 17, A-1090, Wien, Austria

    H. Lassmann

  2. Department of Neurorehabilitation, University of Vienna, Austria

    K. Vass

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Lassmann, H., Vass, K. Are current immunological concepts of multiple sclerosis reflected by the immunopathology of its lesions?. Springer Semin Immunopathol 17, 77–87 (1995). https://doi.org/10.1007/BF00194101

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