Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin


EXPERIMENTAL autoimmune encephalomyelitis (EAE) is an inflammatory condition of the central nervous system with similarities to multiple sclerosis1,2. In both diseases, circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis3–5. We sought to identify the adhesion receptors that mediate the attachment of circulating leukocytes to inflamed brain endothelium in EAE, because this interaction is the first step in leukocyte entry into the central nervous system. Using an in vitro adhesion assay on tissue sections, we found that lymphocytes and monocytes bound selectively to inflamed EAE brain vessels. Binding was inhibited by antibodies against the integrin molecule α4βl, but not by antibodies against numerous other adhesion receptors. When tested in vivo, anti-α4 integrin effectively prevented the accumulation of leukocytes in the central nervous system and the development of EAE. Thus, therapies designed to interfere with α4βl integrin may be useful in treating inflammatory diseases of the central nervous system, such as multiple sclerosis.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Paterson, P. Y. in Textbook of Immunopathology (eds Miescher, P. A. & Mueller-Eberhard, H. J.) 179–213 (Grune & Stratton, New York, 1976).

    Google Scholar 

  2. Alvord, E. C. Jr (ed.) Experimental Allergic Encephalomyelitis: A Useful Model for Multiple Sclerosis 1–511 (Liss, New York, 1984).

  3. Wisniewski, H. M. & Keith, A. B. Ann. Neurol. 1, 144–148 (1977).

    Article  CAS  Google Scholar 

  4. Traugott, U., McFarlin, D. E. & Raine, C. S. Cell Immun. 99, 395–410 (1986).

    Article  CAS  Google Scholar 

  5. Zamvil, S. S. & Steinman, L. A. Rev. Immun. 8, 579–621 (1990).

    Article  CAS  Google Scholar 

  6. Ben-Nun, A., Wekerle, H. & Cohen, I. R. Eur. J. Immun. 11, 195–199 (1981).

    Article  CAS  Google Scholar 

  7. Hickey, W. F., Hsu, B. L. & Kimura, H. J. Neurosci. Res. 28, 254–260 (1991).

    Article  CAS  Google Scholar 

  8. Stamper, H. B. & Woodruff, J. J. J. exp. Med 144, 828–833 (1976).

    Article  Google Scholar 

  9. Hynes, R. O. Cell 48, 549–554 (1987).

    Article  CAS  Google Scholar 

  10. Hemler, M. E. A. Rev. Immun. 8, 365–400.

  11. Elices, M. J. et al. Cell 60, 577–584 (1990).

    Article  CAS  Google Scholar 

  12. Schwartz, B. R., Wayner, E. A., Carlos, T. M., Ochs, H. D. & Harlan, J. M. J. clin. Invest. 85, 2019–2022 (1990).

    Article  CAS  Google Scholar 

  13. Rice, G. E., Munro, J. M. & Bevilacqua, M. P. J. exp. Med. 171, 1369–1374 (1990).

    Article  CAS  Google Scholar 

  14. Pulido, R. et al. J. biol. chem. 266, 10241–10245 (1991).

    CAS  PubMed  Google Scholar 

  15. Briscoe, D. M. et al. Transplantation 51, 537–539 (1991).

    Article  CAS  Google Scholar 

  16. Koch, A. E. et al. Lab. Invest. 64, 313–320 (1991).

    CAS  PubMed  Google Scholar 

  17. Gallatin, W. M., Weissman, I. L. & Butcher, E. C. Nature 304, 30–34 (1983).

    Article  ADS  CAS  Google Scholar 

  18. Jalkanen, S., Bargatze, R. F., de los Toyos, J. & Butcher, E. C. J. Cell Biol. 105, 983–990 (1987).

    Article  CAS  Google Scholar 

  19. Picker, L. J., Nakache, M. & Butcher, E. C. J. Cell Biol. 109, 927–937 (1989).

    Article  CAS  Google Scholar 

  20. Chin, Y.-H., Cai, J.-P. & Johnson, K. J. Immun. 145, 3669–3677 (1990).

    CAS  PubMed  Google Scholar 

  21. Lawrence, M. B. & Springer, T. A. Cell 65, 859–874 (1991).

    Article  CAS  Google Scholar 

  22. Luscinskas, F. W. et al. J. Immun. 146, 1617–1625 (1991).

    CAS  PubMed  Google Scholar 

  23. Diamond, M. S., Staunton, D. E., Marlin, S. D. & Springer, T. A. Cell 65, 961–972 (1991).

    Article  CAS  Google Scholar 

  24. Raine, C. S., Cannella, B., Duijvestijn, A. M. & Cross, A. H. Lab. Invest. 63, 476–490 (1990).

    CAS  PubMed  Google Scholar 

  25. Wilcox, C. E. et al. J. Neuroimmun. 30, 43–51 (1990).

    Article  CAS  Google Scholar 

  26. Cannella, B., Cross, A. H. & Raine, C. S. J. exp. Med. 172, 1521–1524 (1990).

    Article  CAS  Google Scholar 

  27. Ferguson, T. A., Mizutani, H. & Kupper, T. S. Proc. natn. Acad. Sci. U.S.A. 88, 8072–8076 (1991).

    Article  ADS  CAS  Google Scholar 

  28. Damle, N. K. & Aruffo, A. Proc natn. Acad. Sci. U.S.A. 88, 6403–6407 (1991).

    Article  ADS  CAS  Google Scholar 

  29. Nojima, Y. et al. J. exp. Med. 172, 1185–1192 (1990).

    Article  CAS  Google Scholar 

  30. Yednock, T. A., Butcher, E. C., Stoolman, L. M. & Rosen, S. D. J. Cell Biol. 104, 725–731 (1987).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yednock, T., Cannon, C., Fritz, L. et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against α4βl integrin. Nature 356, 63–66 (1992).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing