Abstract
ONE mechanism by which the immune system develops the ability to discriminate self from nonself is the deletion of autoreactive T-cell clones during thymic maturation1–4. The drug cyclosporin A (CsA) has been shown to interfere with this process, allowing the escape of normally 'forbidden' T-cell clones5,6 and the appearance of autoimmune disease7–10. Recently, it has been demonstrated that immature thymocytes undergo programmed cell death (apoptosis) upon activation via the T-cell receptor11. A similar phenomenon of activation-induced cell death (AICD) has been observed in T-cell hybridomas12,13. Here we show that AICD in T-cell hybridomas in vitro and in thymocytes in vivo is blocked by CsA. Thus, clonal deletion may involve AICD when self-reactive, immature T cells are induced by self antigen, and CsA may cause autoimmunity by interfering with this process.
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References
Kappler, J. W. et al. Cell 49, 263–271 (1987).
Kappler, J. W., Staerz, U., White, J. & Marrack, P. Nature 332, 35–40 (1988).
MacDonald, H. R. et al. Nature 332, 40–45 (1988).
Kisielow, P., Bluthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).
Gao, E.-K., Lo, D., Cheney, R., Kanagawa, O. & Sprent, J. Nature 336, 176–179 (1988).
Jenkins, M. K., Schwartz, R. H. & Pardoll, D. M. Science 241, 1655–1658 (1988).
Glazer, A., Tutschha, P. J., Farmer, E. R. & Santos, G. W. J. exp. Med. 158, 1–8 (1983).
Hess, A. D. et al. J. exp. Med. 161, 718–730 (1985).
Cheney, R. T. & Sprent, J. Transplant proc. 17, 528–530 (1985).
Sakaguchi, S. & Sakaguchi, N. J. exp. Med. 167, 1479–1485 (1988).
Smith, C. A., Williams, G. T., Kingston, R., Jenkinson, E. J. & Owen, J. J. Nature 337, 181–184 (1989).
Ashwell, J. D., Cunningham, R. E., Noguchi, P. D. & Hernandez, D. J. exp. Med. 165, 173–194 (1987).
Mercep, M., Bluestone, J. A., Noguchi, P. D. & Ashwell, J. D. J. Immun. 140, 324–335 (1988).
Shevach, E. M. A. Rev. Immun. 3, 397–424 (1985).
Fotedar, A. et al. J. Immun. 135, 3028–3033 (1985).
Mossmann, T. R. J. Immun. meth. 65, 55–63 (1983).
Leo, O., Foo, M., Sachs, D. H., Samelson, L. E. & Bluestone, J. A. Proc. natn. Acad. Sci. U.S.A. 84, 1374–1378 (1987).
Butcher, E. C. & Ford, W. L. in Handbook of Experimental Immunology Vol. 2, Cellular Immunology (eds Weir, D. M., Herzenberg, L. A., Blackwell, C. & Herzenberg, L. A.) 57.13–57.15. (Blackwell, Oxford, 1986).
Wyllie, A. H. Arch. Toxicol. 11, (Suppl.) 3–10 (1987).
Walker, N. I., Harmon, B. V., Gobe, G. C. & Kerr, J. F. R. Meth. Achieve. exp. Path. 13, 18–54 (1988).
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Shi, Y., Sahai, B. & Green, D. Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes. Nature 339, 625–626 (1989). https://doi.org/10.1038/339625a0
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DOI: https://doi.org/10.1038/339625a0
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