Abstract
Cyclosporin A (CsA) acts as a powerful immunosuppressive agent, and also, when given in repeated doses, can cause T-cell-dependent graft-versus-host disease and organ-specific autoimmune disease in rodents1–6. This suggests that CsA interferes with the processes governing self-tolerance1, either by nullifying the activity of T suppressor cells4,6 or by preventing the deletion of autoreactive T cells during ontogeny in the thymus2. We report here that irradiated mice given repeated injections of CsA show striking dysfunction of the thymus. There are two different effects, the first of which is that CsA seems to block the differentiation of immature CD4+CD8+ thymocytes into mature CD4+CD8- and CD4-CD8+ cells expressing a high density of T-cell receptors and CD3 molecules. Second, CsA-treated mice show incomplete deletion of T cells expressing T-cell receptor molecules reactive to self H–2 I–E molecules.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Glazier, A., Tutschka, R. J., Farmer, E. R. & Santos, G. W. J. exp. Med. 158, 1–8 (1983).
Cheney, R. T. & Sprent, J. Transplantn Proc. 17, 528–530 (1985).
Hess, A. D., Horwitz, L., Beschorner, W. E. & Santos, G. W. J. exp. Med. 161, 718–730 (1985).
Sorokin, R., Kimura, H., Schroder, K., Wilson, D. H. & Wilson, D. B. J. exp. Med. 164, 1615–1625 (1986).
Beschorner, W. E., Hess, A. D., Shinn, C. H. & Santos, G. W. Transplantation 45, 209–215 (1988).
Sakaguchi, S. & Sakaguchi, N. J. exp. Med. 167, 1479–1485 (1988).
Mathieson, B. J. & Fowlkes, B. J. Immunol. Rev. 82, 141–173 (1984).
Scollay, R., Bartlett, P. & Shortman, K. Immunol. Rev. 82, 79–103 (1984).
von Boehmer, H. Curr. Top. Microbiol. Immun. 126, 19–25 (1986).
Sprent, J. & Webb, S. R. Adv. Immun. 41, 39–133 (1987).
Roehm, N. et al. Cell 38, 577–584 (1984).
Bluestone, J. A., Pardoll, D., Sharrow, S. O. & Fowlkes, B. J. Nature 326, 82–84 (1987).
Kisielow, P., Bluthmann, H., Staerz, U., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).
Fowlkes, B. J., Schwartz, R. H. & Pardoll, D. M. Nature 334, 620–623 (1988).
Scollay, R. G., Butcher, E. C. & Weissman, I. L. Eur. J. Immun. 10, 210–218 (1980).
MacDonald, H. R., Budd, R. C. & Howe, R. C. Eur. J. Immun. 18, 519–523 (1988).
Thomson, A. W., Whiting, P. H., Blair, J. T., Davidson, J. L. & Simpson, J. G. Transplantation 32, 271–277 (1981).
Hattori, A., Kunz, H. W., Gill, T. G. III & Shinozuka, H. Am. J. Path. 128, 111–120 (1987).
Beschorner, W. E., Olson, J. L., Hess, A. D., DiGennaro, K. A. & Santos, G. W. Transplantation 45, 797–803 (1988).
Bruce, J., Symington, F. W., McKearn, T. J. & Sprent, J. J. Immun. 127, 2496–2501 (1981).
Kappler, J. W., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).
Shevach, E. M. A. Rev. Immun. 3, 397–423 (1985).
Sprent, J., Schaefer, M., Lo, D. & Korngold, R. J. exp. Med. 163, 998–1011 (1986).
Sprent, J. & Schaefer, M. J. exp. Med. 162, 2068–2088 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Gao, EK., Lo, D., Cheney, R. et al. Abnormal differentiation of thymocytes in mice treated with cyclosporin A. Nature 336, 176–179 (1988). https://doi.org/10.1038/336176a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/336176a0
This article is cited by
-
Biological effects of cyclosporin A on CD3−CD161+ and CD3+CD161+ lymphocytes
Molecular and Cellular Biochemistry (2019)
-
Calcium signaling in immune cells
Nature Immunology (2009)
-
Autologous graft-versus-host disease: harnessing anti-tumor immunity through impaired self-tolerance
Bone Marrow Transplantation (2008)
-
NFAT proteins: key regulators of T-cell development and function
Nature Reviews Immunology (2005)
Comments
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.