Skip to main content
SpringerLink
Log in

Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions

  • Regular Papers
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Summary

The effect of a circulating monoclonal antibody recognizing an antigen located on the surface of myelin sheaths (myelin/oligodendroglia glycoprotein, MOG) on clinical and histopathological expression of experimental allergic encephalomyelitis (EAE) was tested in a model of EAE passively transferred by monospecific T lymphocytes. Intravenous injection of anti-MOG antibody at the onset of the disease massively augmented clinical impairment as well as primary demyelination. The structure of the CNS lesions depended on the balance between encephalitogenic T cells and anti-MOG antibody: when EAE was induced with high numbers of T cells, circulating anti-MOG antibody resulted in ubiquitous perivenous demyelination in the spinal cord and medulla oblongata. On the contrary, focal confluent demyelinated lesions were observed in animals injected with low numbers of T cells (even as few as 104) and anti-MOG antibody. Our studies, thus, indicate that the formation of inflammatory demyelinating lesions may be due to a synergistic action of cellular and humoral immune mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alvord EC (1970) Acute disseminated encephalomyelitis and allergic neuroencephalopathies. In: Vinken PI, Bruyn GW (eds) Handbook of clinical neurology, vol. 9. Elsevier, New York, pp 500–571

    Google Scholar 

  2. Ben-Nun A, Wekerle H, Cohen IR (1981) The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol 11:195–199

    Google Scholar 

  3. Bornstein MB, Appel SH (1961) The application of tissue culture to the study of experimental allergic encephalomyelitis. I. Patterns of demyelination. J Neuropathol Exp Neurol 20:141–147

    Google Scholar 

  4. Bornstein MB, Appel SH (1965) Tissue culture studies in demyelination. Ann NY Acad Sci 122:280–286

    Google Scholar 

  5. Bourdette DN, Driscoll BF, Seil FJ, Kies MW, Alvord EC (1986) Severity of demyelination in vivo correlates with serum myelination inhibition activity in guinea pigs having a new form of experimental allergic encephalomyelitis. Neurochem Pathol 4:1–9

    Google Scholar 

  6. Bradbury K, Suckling AJ (1984) The nature of factors in relapsing EAE and MS sera which induce myelinotoxicity and cellular changes in organ culture. In: Alvord EC, Kies MW, Suckling AJ (eds) Experimental allergic encephalomyelitis: a useful model for multiple sclerosis. Alan Liss, New York, pp 193–199

    Google Scholar 

  7. Brosnan CF, Stoner GL, Bloom BR, Wisniewski HM (1977) Studies on demyelination in the rabbit eye. II. Antibody-dependent cell-mediated demyelination. J Immunol 118: 2103–2110

    Google Scholar 

  8. Brosnan CF, Cammer W, Norton WT, Bloom BR (1980) Proteinase inhibitors suppress the development of experimental allergic encephalomyelitis. Nature 285:235–237

    Google Scholar 

  9. Brosnan CF, Bornstein MB, Bloom BR (1981) The effects of macrophage depletion on the clinical and pathological expression of experimental allergic encephalomyelitis. J Immunol 126:614–620

    Google Scholar 

  10. Brosnan CF, Traugott U, Raine CS (1983) Analysis of humoral and cellular events and the role of lipid haptens during CNS demyelination. Acta Neuropathol (Berl) [Suppl] 9:59–70

    Google Scholar 

  11. Cambi F, Lees MB, Williams RM, Macklin WB (1983) Chronic experimental allergic encephalomyelitis produced by bovine proteolipid apoprotein: immunological studies in rabbits. Ann Neurol 13:303–308

    Google Scholar 

  12. Cohen JA, Essayan DM, Zweiman B, Lisak RP (1987) Limiting dilutions of the frequency of antigen-reactive lymphocytes isolated from the central nervous system of Lewis rats with experimental allergic encephalomyelitis. Cell Immunol 108:203–213

    Google Scholar 

  13. Dubois-Dalq M, Niedieck B, Buyse M (1970) Action of anti-cerebroside sera on myelinated nervous tissue culture. Pathol Eur 5:331–347

    Google Scholar 

  14. Fallis RJ, Powers LM, Sy MS, Weiner HL (1987) Adoptive transfer of murine chronic relapsing autoimmune encephalomyelitis: analysis of basic protein reactive cells in lymphoid organs and nervous system of donor and recipient animals. J Neuroimmunol 14:205–219

    Google Scholar 

  15. Glynn P, Weedon D, Cuzner ML (1986) Chronic experimental autoimmune encephalomyelitis. Circulating auto-antibodies bind predominantly determinants expressed by complexes of basic protein and lipids of myelin. J Neurol Sci 73:111–123

    Google Scholar 

  16. Grundke-Iqbal I, Bornstein MB (1980) Multiple sclerosis: serum gamma globulin and demyelination in organ culture. Neurology 30:749–754

    Google Scholar 

  17. Hashim GA, Wood DD, Moscarello MA (1980) Myelin Lipophilin-induced demyelinating disease of the central nervous system. Neurochem Res 5:1137–1145

    Google Scholar 

  18. Kies MW, Murphy JB, Alvord EC (1960) Fractionation of guinea pig brain proteins with encephalitogenic activity. Fed Proc 19:207 (abstr)

    Google Scholar 

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

    Google Scholar 

  20. 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) 55:297–306

    Google Scholar 

  21. Lassmann H, Stemberger H, Kitz K, Wisniewski HM (1983) In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis. J Neurol Sci 59:123–137

    Google Scholar 

  22. Lassmann H, Suchanek G, Kitz K, Stemberger H, Schwerer B, Bernheimer H (1984) Antibodies in the pathogenesis of demyelination in chronic relapsing EAE (cr-EAE). In: Alvord EC, Kies MW, Suckling AJ (eds) Experimental allergic encephalomyelitis: a useful model for multiple sclerosis. Alan Liss, New York, pp 165–170

    Google Scholar 

  23. Lassmann H, Vass K, Brunner C, Seitelberger F (1986) Characterization of inflammatory infiltrates in experimental allergic encephalomyelitis. Prog Neuropathol 6:33–62

    Google Scholar 

  24. Linington C, Lassmann H (1987) Antibody response in chronic relapsing experimental allergic encephalomyelitis: correlation of the serum demyelinating activity and the antibody titer to the myelin oligodendrocyte glycoprotein (MOG). J Neuroimmunol 17:61–69

    Google Scholar 

  25. Linington C, Webb M, Woodhams PL (1984) A novel myelin associated glycoprotein defined by a mouse monoclonal antibody. J Neuroimmunol 6:387–396

    Google Scholar 

  26. Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein (MOG). Am J Pathol (in press)

  27. Olsson T, Henrikson A, Link H, Kristensson K (1984) IgM and IgG responses during chronic relapsing experimental allergic encephalomyelitis (r-EAE). J Neuroimmunol 6: 265–281

    Google Scholar 

  28. Paterson PY (1960) Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med 111:119–135

    Google Scholar 

  29. Prineas JW (1986) The neuropathology of multiple sclerosis. In: Koetsier JC (ed) Handbook of clinical neurology, vol 47. Elsevier, New York, pp 213–257

    Google Scholar 

  30. Raine CS (1986) Experimental allergic encephalomyelitis and experimental allergic neuritis. In: Koetsier JC (ed) Handbook of clinical neurology, vol 47. Elsevier, New York, pp 429–466

    Google Scholar 

  31. Roth GA, Röyttä M, Yu RK, Raine CS, Bornstein MB (1985) Antisera to different glycolipids induce myelin alterations in mouse spinal cord tissue cultures. Brain Res 339:9–18

    Google Scholar 

  32. Schlüsener HJ (1986) Inhibition of rat autoimmune T cell activation by monoclonal antibodies. J Neuroimmunol 11:261–270

    Google Scholar 

  33. Schwerer B, Kitz K, Lassmann H, Bernheimer H (1984a) Serum antibodies against glycosphingolipids in chronic relapsing experimental allergic encephalomyelitis. Demonstration by ELISA and relation to serum in vivo demyelinating activity. J Neuroimmunol 7:107–119

    Google Scholar 

  34. Schwerer B, Schuller-Levis GB, Mehta PD, Madrid RE, Wisniewski HM (1984b) Cellular and humoral immune response to MBP during the course of chronic relapsing EAE. In: Alvord EC, Kies MW, Suckling AJ (eds) Experimental allergic encephalomyelitis: a useful model for multiple sclerosis. Alan Liss, New York, pp 187–192

    Google Scholar 

  35. Schwerer B, Lassmann H, Kitz K, Bernheimer H (1986) Ganglioside GM1, a molecular target for immunological and toxic attacks: similarity of neuropathological lesions induced by ganglioside antiserum and cholera toxin. Acta Neuropathol (Berl) 72:55–61

    Google Scholar 

  36. Sergott RC, Brown MJ, Silberberg DH, Lisak RP (1984) Anti-galactocerebroside serum demyelinates optic nerve in vivo. J Neurol Sci 64:297–303

    Google Scholar 

  37. Vass K, Lassmann H, Wekerle H, Wisniewski HM (1986) The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 70:149–160

    Google Scholar 

  38. Wekerle H (1984) The lesion of acute experimental autoimmune encephalomyelitis. Isolation and membrane phenotypes of perivascular infiltrates from encephalitic rat brain white matter. Lab Invest 51:199–205

    Google Scholar 

  39. Wekerle H, Fierz W (1985) T cell approach to demyelinating disease. Springer Semin Immunopathol 8:97–110

    Google Scholar 

  40. Wekerle H, Schwab M, Linington C, Meyerman R (1986) Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes. Eur J Immunol 16:1551–1557

    Google Scholar 

  41. Williams RM, Krakowka S, Koestner A (1980) In vivo demyelination by antimyelin antibodies. Acta Neuropathol (Berl) 50:1–8

    Google Scholar 

  42. Wisniewski HM, Lassmann H, Brosnan CF, Mehta PD, Lidsky AA, Madrid RE (1982) Multiple sclerosis: immunological and experimental aspects. In: Matthews WB, Glaser GH (eds) Recent advances in clinical neurology, vol 3. Churchill-Livingstone, London, pp 95–124

    Google Scholar 

Download references

Author information

Authors and Affiliations

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

    H. Lassmann & C. Brunner

  2. Institute of Brain Research, Austrian Academy of Sciences, Vienna, Austria

    H. Lassmann & C. Brunner

  3. Max-Planck-Society, Clinical Research for Multiple Sclerosis, D-8700, Würzburg, Germany

    M. Bradl

  4. Department of Neurology, University of Cardiff, UK

    C. Linington

Authors
  1. H. Lassmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Brunner
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Bradl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Linington
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the Science Research Fund (Austria), Project P5354 and P6438M

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lassmann, H., Brunner, C., Bradl, M. et al. Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol 75, 566–576 (1988). https://doi.org/10.1007/BF00686201

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00686201

Key words

Search

Navigation