Autoimmunity in Multiple Sclerosis: Do we have an Experimental Model?

  • Marian W. Kies
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 100)


Experimental autoimmunity of the CNS has been well characterized — the antigen has been identified, effector cell specificity has been defined, and the relationship between cellular sensitization and antibody production has been partially clarified. In the guinea pig, experimental allergic encephalomyelitis (EAE) is induced by one injection of myelin basic protein in complete Freun ds adjuvant (BP/CFA). If BP/CFA is preceded by repeated injections of basic protein in incomplete Freun’s adjuvant(BP/IFA), EAE is not induced; the guinea pigs survive and ultimately produce antibody. Induction and prevention of EAE as well as antibody induction by this schedule are dependent on the presence of the intact encephalitogenic (T-cell) site in the polypeptide used for sensitization and preimmunization. In contrast, B-cell sites (those peptide sequences which bind antibody) are independent of the T-cell site. At least 5 specific antigenic regions (B-cell sites) have been demonstrated in the BP molecule. High mycobacteria levels bypass the specificity requirement of helper T-cells but cannot bypass the specificity requirement of effector T-cells. In spite of the sophisticated immunologic techniques available, our knowledge of humoral and cellular sensitivity in multiple sclerosis (MS) patients is very limited. The experimental demonstration of an analogy between EAE and MS is weak: a) Demonstration of BP-sensitized cells or BP-specific antibodies in peripheral blood of MS patients has not been successful. b) Anti-myelin serum factors reported to be associated with both disease states (experimental autoimmunity and MS) are clearly not identical. Nevertheless, successful treatment of EAE in animals by BP/IFA injections has encouraged consideration of clinical trials to test the therapeutic value of BP injections in MS patients. If successful, the question will be answered: if unsuccessful, the dilemma still remains.


Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Myelin Basic Protein Disease Index 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Alvord, E.C., Jr., Acute disseminated encephalomyelitis and “allergic” neuro-encephalopathies, in Handbook of Clinical Neurology (P.J. Vinken and G.W. Bruyn, eds.) North-Holland Publishing Co.,Amsterdam (1970) pp. 500–571.Google Scholar
  2. 2.
    Alvord, E.C., Jr., Shaw, C.-M., Hrugy, S. and Kies, M.W., Encephalitogen-induced inhibition of experimental allergic encephalomyelitis: prevention, suppression and therapy, Ann. N. Y. Acad. Sci. 122 (1965) 333–345.PubMedCrossRefGoogle Scholar
  3. 3.
    Bernard, C.C.A., Suppressor T cells prevent experimental autoimmune encephalomyelitis in mice, Clin. Exp. Immunol. 29 (1977) 100–109.PubMedGoogle Scholar
  4. 4.
    Bernard, C.C.A., MacKay, I.R., Whittingham, S. and Brous, P., Durability of immune protection against experimental autoimmune encephalomyelitis, Cell. Immunol. 22 (1976) 297–310.PubMedCrossRefGoogle Scholar
  5. 5.
    Carnegie, P.R., Amino acid sequence of the encephalitogenic basic protein from human myelin, Biochem. J. 123 (1971) 57–67.PubMedGoogle Scholar
  6. 6.
    Chao, L.-P. and Einstein, E.R., Localization of the active site through chemical modification of the encephalitogenic protein, J. Biol. Chem. 245 (1970) 6397–6403.PubMedGoogle Scholar
  7. 7.
    Coates, A., MacKay, I.R. and Crawford, M., Immune protection against experimental autoimmune encephalomyelitis: optimal conditions and analysis of mechanism, Cell. Immunol. 12 (1974) 370–381.PubMedCrossRefGoogle Scholar
  8. 8.
    Driscoll, B.F., Kies, M.W. and Alvord, E.C., Jr., Successful treatment of experimental allergic encephalomyelitis (EAE) in guinea pigs with homologous myelin basic protein, J. Immunol. 112 (1974) 392–397.PubMedGoogle Scholar
  9. 9.
    Driscoll, B.F., Kies, M.W. and Alvord, E.C., Jr., Adoptive transfer of experimental allergic encephalomyelitis (EAE): prevention of successful transfer by treatment of donors with myelin basic protein, J. Immunol. 114 (1975) 291–292.PubMedGoogle Scholar
  10. 10.
    Driscoll, B.F., Kies, M.W. and Alvord, E.C., Jr., Protection against experimental allergic encephalomyelitis with peptides derived from myelin basic protein: presence of intact encephalitogenic site is essential, J. Immunol. 117 (1976) 110–114.PubMedGoogle Scholar
  11. 11.
    Eylar, E.H., Brostoff, S., Hashim, G., Caccam, J. and Burnett, P., Basic Al protein of the myelin membrane. The complete amino acid sequence, J. Biol. Chem. 246 (1971) 5770–5784.PubMedGoogle Scholar
  12. 12.
    Eylar, E.H., Jackson, J., Rothenberg, B. and Brostoff, S.W., Suppression of the immune response: reversal of the disease state with antigen in allergic encephalomyelitis, Nature 236 (1972) 74–76.PubMedCrossRefGoogle Scholar
  13. 13.
    Falk, G.A., Kies, M.W. and Alvord, E.C., Jr., Delayed hypersensitivity to myelin basic protein in the passive transfer of experimental allergic encephalomyelitis, J. Immunol. 101 (1968) 638–644.PubMedGoogle Scholar
  14. 14.
    Gonatas, N.K. and Howard, J.C., Inhibition of experimental allergic encephalomyelitis in rats severely depleted of T cells, Science 186 (1974) 839–841.PubMedCrossRefGoogle Scholar
  15. 15.
    Kies, M.W., Experimental allergic encephalomyelitis, in Biology of Brain Dysfunction ( G.E. Gaull, ed.) Plenum Press, New York (1973) pp. 185–224.CrossRefGoogle Scholar
  16. 16.
    Kies, M.W. and Alvord, E.C., Jr., Prevention of allergic encephalomyelitis by prior injection of adjuvants, Nature 182 (1958) 1106.PubMedCrossRefGoogle Scholar
  17. 17.
    Kies, M.W. and Alvord, E.C., Jr., Encephalitogenic activity in guinea pigs of water-soluble protein fractions of nervous tissue, in“Allergic” Encephalomyelitis (M.W. Kies and E.C. Alvord, Jr., eds.) Charles C. Thomas, Springfield, Ill. (1959) pp. 293–299.Google Scholar
  18. 18.
    Laatsch, R.H., Kies, M.W., Gordon, S. and Alvord, E.C., Jr., The encephalitogenic activity of myelin isolated by ultracentrifugation, J. Exp. Med. 115 (1962) 777–788.PubMedCrossRefGoogle Scholar
  19. 19.
    Levine, S., Sowinski, R. and Kies, M.W., Treatment of experimental allergic encephalomyelitis with encephalitogenic basic proteins, Proc. Soc. Exp. Biol. Med. 139 (1972) 506–510.PubMedGoogle Scholar
  20. 20.
    Lisak, R.P. and Kies, M.W., Mycobacterial suppression of delayed hypersensitivity in experimental allergic encephalomyelitis, Proc. Soc. Exp. Biol. Med. 128 (1968) 214–218.Google Scholar
  21. 21.
    MacPherson, C.F.C. and Yo, S.-L., Studies on brain antigens. VI. Prevention of experimental allergic encephalomyelitis by a water-soluble spinal cord protein,B1-SCP, J. Immunol. 110 (1973) 1371–1375.PubMedGoogle Scholar
  22. 22.
    Ortiz -Ortiz, L. and Weigle, W.O., Cellular events in the induction of experimental allergic encephalomyelitis in rats, J. Exp. Med. 144 (1976) 604–616.PubMedCrossRefGoogle Scholar
  23. 23.
    Shaw, C.-M., Alvord, E.C., Jr., Kaku, J. and Kies, M.W., Correlation of experimental allergic encephalomyelitis with delayed-type skin sensitivity to specific homologous encephalitogen, Ann. N.Y. Acad. Sci. 122 (1965) 318–331.PubMedCrossRefGoogle Scholar
  24. 24.
    Swanborg, R.H., Antigen-induced inhibition of experimental allergic encephalomyelitis. I. Inhibition in guinea pigs injected with non-encephalitogenic modified myelin basic protein, J. Immunol. 109 (1972) 540–546.PubMedGoogle Scholar
  25. 25.
    Swanborg, R.H., Antigen-induced inhibition of experimental allergic encephalomyelitis. III. Localization of an inhibitory site distinct from the major encephalitogenic determinant of myelin basic protein, J. Immunol. 114 (1975) 191–194.PubMedGoogle Scholar
  26. 26.
    Swierkosz, J.E. and Swanborg, R.H., Suppressor cell control of unresponsiveness to experimental allergic encephalomyelitis J. Immunol. 115 (1975) 631–633.PubMedGoogle Scholar
  27. 27.
    Teitelbaum, D., Meshorer, A., Hirshfield, T.,Arnon, R. and Sela, M., Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide, Eur. J. Immunol. 1 (1971) 242–248.PubMedCrossRefGoogle Scholar
  28. 28.
    Whipple, H.E., ed., Research in Demyelinating Diseases, Ann. N. Y. Acad. Sci. 122 (1965) 1–570.Google Scholar
  29. 29.
    Witebsky, E., The status of organ specificity, in “Allergic” Encephalomyelitis ( M.W. Kies and E.C. Alvord, eds.) Charles C. Thomas, Springfield, Ill. (1959) pp. 321–347.Google Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • Marian W. Kies
    • 1
  1. 1.Section on Myelin Chemistry, Laboratory of Cerebral MetabolismNational Institute of Mental HealthBethesdaUSA

Personalised recommendations