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The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1990 Jun 1;171(6):1943–1955. doi: 10.1084/jem.171.6.1943

Prevention and treatment of murine experimental allergic encephalomyelitis with T cell receptor V beta-specific antibodies

PMCID: PMC2187969  PMID: 1693655

Abstract

Experimental allergic encephalomyelitis (EAE) is a model system for T cell-mediated autoimmune disease. Symptoms of EAE are similar to those of multiple sclerosis (MS) in humans. EAE is induced in susceptible animal strains by immunization with myelin basic protein (MBP) and potent adjuvant. The major T cell response to MBP in B10.PL mice is directed towards an NH2-terminal epitope and involves T cells expressing either V beta 8.2 or V beta 13 gene segments. Animals treated with a TCR V beta 8-specific mAb have a reduced incidence of EAE. We report here that the in vivo administration of a combination of anti-V beta 8.2 and anti-V beta 13 mAbs results in a long-term elimination of T cells involved in the response to MBP. When given before MBP immunization, anti-TCR antibody treatment leads to nearly complete protection against EAE. Antibody treatment also results in a dramatic reversal of paralysis in diseased animals. Thus, treatment with a combination of V beta-specific antibodies is a very effective therapy for the prevention and treatment of EAE. It is hoped that the future characterization of TCR V gene usage in human autoimmune diseases may lead to similar strategies of immune intervention.

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Selected References

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  1. Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
  2. Behlke M. A., Chou H. S., Huppi K., Loh D. Y. Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986 Feb;83(3):767–771. doi: 10.1073/pnas.83.3.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ben-Nun A., Wekerle H., Cohen I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol. 1981 Mar;11(3):195–199. doi: 10.1002/eji.1830110307. [DOI] [PubMed] [Google Scholar]
  4. Brostoff S. W., Mason D. W. Experimental allergic encephalomyelitis: successful treatment in vivo with a monoclonal antibody that recognizes T helper cells. J Immunol. 1984 Oct;133(4):1938–1942. [PubMed] [Google Scholar]
  5. Fritz R. B., Chou C. H., McFarlin D. E. Induction of experimental allergic encephalomyelitis in PL/J and (SJL/J x PL/J)F1 mice by myelin basic protein and its peptides: localization of a second encephalitogenic determinant. J Immunol. 1983 Jan;130(1):191–194. [PubMed] [Google Scholar]
  6. Holda J. H., Welch A. M., Swanborg R. H. Autoimmune effector cells. I. Transfer of experimental encephalomyelitis with lymphoid cells cultured with antigen. Eur J Immunol. 1980 Aug;10(8):657–659. doi: 10.1002/eji.1830100815. [DOI] [PubMed] [Google Scholar]
  7. Howell M. D., Winters S. T., Olee T., Powell H. C., Carlo D. J., Brostoff S. W. Vaccination against experimental allergic encephalomyelitis with T cell receptor peptides. Science. 1989 Nov 3;246(4930):668–670. doi: 10.1126/science.2814489. [DOI] [PubMed] [Google Scholar]
  8. Lassmann H., Wisniewski H. M. Chronic relapsing experimental allergic encephalomyelitis: clinicopathological comparison with multiple sclerosis. Arch Neurol. 1979 Aug;36(8):490–497. doi: 10.1001/archneur.1979.00500440060011. [DOI] [PubMed] [Google Scholar]
  9. McDuffie M., Born W., Marrack P., Kappler J. The role of the T-cell receptor in thymocyte maturation: effects in vivo of anti-receptor antibody. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8728–8732. doi: 10.1073/pnas.83.22.8728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mokhtarian F., McFarlin D. E., Raine C. S. Adoptive transfer of myelin basic protein-sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature. 1984 May 24;309(5966):356–358. doi: 10.1038/309356a0. [DOI] [PubMed] [Google Scholar]
  11. Ortiz-Ortiz L., Weigle W. O. Cellular events in the induction of experimental allergic encephalomyelitis in rats. J Exp Med. 1976 Sep 1;144(3):604–616. doi: 10.1084/jem.144.3.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Owhashi M., Heber-Katz E. Protection from experimental allergic encephalomyelitis conferred by a monoclonal antibody directed against a shared idiotype on rat T cell receptors specific for myelin basic protein. J Exp Med. 1988 Dec 1;168(6):2153–2164. doi: 10.1084/jem.168.6.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. PATERSON P. Y. Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med. 1960 Jan 1;111:119–136. doi: 10.1084/jem.111.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pettinelli C. B., Fritz R. B., Chou C. H., McFarlin D. E. Encephalitogenic activity of guinea pig myelin basic protein in the SJL mouse. J Immunol. 1982 Sep;129(3):1209–1211. [PubMed] [Google Scholar]
  15. Pettinelli C. B., McFarlin D. E. Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: requirement for Lyt 1+ 2- T lymphocytes. J Immunol. 1981 Oct;127(4):1420–1423. [PubMed] [Google Scholar]
  16. Raine C. S., Snyder D. H., Valsamis M. P., Stone S. H. Chronic experimental allergic encephalomyelitis in inbred guinea pigs. An ultrastructural study. Lab Invest. 1974 Oct;31(4):369–380. [PubMed] [Google Scholar]
  17. Richert J. R., Driscoll B. F., Kies M. W., Alvord E. C., Jr Adoptive transfer of experimental allergic encephalomyelitis: incubation of rat spleen cells with specific antigen. J Immunol. 1979 Feb;122(2):494–496. [PubMed] [Google Scholar]
  18. Sriram S., Steinman L. Anti I-A antibody suppresses active encephalomyelitis: treatment model for diseases linked to IR genes. J Exp Med. 1983 Oct 1;158(4):1362–1367. doi: 10.1084/jem.158.4.1362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Steinman L., Rosenbaum J. T., Sriram S., McDevitt H. O. In vivo effects of antibodies to immune response gene products: prevention of experimental allergic encephalitis. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7111–7114. doi: 10.1073/pnas.78.11.7111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Traugott U., McFarlin D. E., Raine C. S. Immunopathology of the lesion in chronic relapsing experimental autoimmune encephalomyelitis in the mouse. Cell Immunol. 1986 May;99(2):395–410. doi: 10.1016/0008-8749(86)90248-0. [DOI] [PubMed] [Google Scholar]
  21. Traugott U., Shevach E., Chiba J., Stone H. J., Raine C. S. Autoimmune encephalomyelitis: simultaneous identification of T and B cells in the target organ. Science. 1981 Dec 11;214(4526):1251–1253. doi: 10.1126/science.7029715. [DOI] [PubMed] [Google Scholar]
  22. Urban J. L., Horvath S. J., Hood L. Autoimmune T cells: immune recognition of normal and variant peptide epitopes and peptide-based therapy. Cell. 1989 Oct 20;59(2):257–271. doi: 10.1016/0092-8674(89)90288-2. [DOI] [PubMed] [Google Scholar]
  23. Urban J. L., Kumar V., Kono D. H., Gomez C., Horvath S. J., Clayton J., Ando D. G., Sercarz E. E., Hood L. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell. 1988 Aug 12;54(4):577–592. doi: 10.1016/0092-8674(88)90079-7. [DOI] [PubMed] [Google Scholar]
  24. Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
  25. Waldor M. K., Sriram S., Hardy R., Herzenberg L. A., Herzenberg L. A., Lanier L., Lim M., Steinman L. Reversal of experimental allergic encephalomyelitis with monoclonal antibody to a T-cell subset marker. Science. 1985 Jan 25;227(4685):415–417. doi: 10.1126/science.3155574. [DOI] [PubMed] [Google Scholar]
  26. Wiśniewski H. M., Keith A. B. Chronic relapsing experimental allergic encephalomyelitis: an experimental model of multiple sclerosis. Ann Neurol. 1977 Feb;1(2):144–148. doi: 10.1002/ana.410010207. [DOI] [PubMed] [Google Scholar]
  27. Wraith D. C., Smilek D. E., Mitchell D. J., Steinman L., McDevitt H. O. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell. 1989 Oct 20;59(2):247–255. doi: 10.1016/0092-8674(89)90287-0. [DOI] [PubMed] [Google Scholar]
  28. Zamvil S. S., Mitchell D. J., Moore A. C., Kitamura K., Steinman L., Rothbard J. B. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature. 1986 Nov 20;324(6094):258–260. doi: 10.1038/324258a0. [DOI] [PubMed] [Google Scholar]
  29. Zamvil S., Nelson P., Trotter J., Mitchell D., Knobler R., Fritz R., Steinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. 1985 Sep 26-Oct 2Nature. 317(6035):355–358. doi: 10.1038/317355a0. [DOI] [PubMed] [Google Scholar]

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