Abstract
FOLLOWING induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87–99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87–99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against inter-leukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-α in the lesion.
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References
Oksenberg, J. R. et al. Nature 362, 68–70 (1993).
Steinman, L. Behring Inst. Mitt. 94, 148–157 (1994).
Martin, R. et al. J. exp. Med. 173, 19–24 (1991).
Gold, D. P. et al. J. Immun. 148, 1712–1717 (1992).
Vogt, A. B. et al. J. Immun. 153, 1665–1673 (1994).
Koop, B. F. et al. Genomics 13, 1209–1230 (1992).
Wucherpfennig, K. W. et al. J. exp. Med. 179, 279–290 (1994).
Wraith, D. C., McDevitt, H. O., Steinman, L. & Acha-Orbea, H. Cell 57, 709–715 (1989).
De Magistris, M. T. et al. Cell 68, 625–634 (1992).
Bell, B. B., Lindsey, J., Sobel, R. A., Hodgkinson, S. & Steinman, L. J. Immun. 150, 4085–4092 (1993).
Selmaj, K. W., Farooq, M., Norton, W. T., Raine, C. S. & Brosnan, C. F. J. Immun. 144, 129–136 (1990).
Powel, M. B. et al. Int. Immun. 2, 539–544 (1990).
Lehmann, P. V., Forsthuber, T., Miller, A. & Sercarz, E. E. Nature 358, 155–157 (1992).
Fiorentino, D. F., Zlotnik, A., Mosmann, T. R., Howard, M. & O'Garra, A. J. Immun. 147, 3815–3822 (1991).
Vassalli, P. Rev. Immun. 10, 411–452 (1992).
Raine, C. S. Nature Med. 1, 211–214 (1995).
Racke, M. et al. J. exp. Med. 180, 1961–1966 (1994).
Cannella, B. & Raine, C. S. Ann. Neurol. 37, 424–435 (1995).
Karin, N. et al. J. exp. Med. 180, 2227–2237 (1994).
Brocke, S. et al. Nature 365, 642–644 (1993).
Platzer, C. et al. Eur. J. Immun. 22, 1179–1184 (1992).
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Brocke, S., Gijbels, K., Allegretta, M. et al. Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein. Nature 379, 343–346 (1996). https://doi.org/10.1038/379343a0
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DOI: https://doi.org/10.1038/379343a0
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