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Effects of cyclosporine A on T cell development and clonal deletion
Abstract
Cyclosporine A (CsA) is an important immunosuppressive drug that is widely used in transplantation medicine. Many of its suppressive effects on T cells appear to be related to the inhibition of T cell receptor (TCR)-mediated activation events. Paradoxically, in certain situations CsA is responsible for the induction of a T cell-mediated autoimmunity. The effects of CsA on T cell development in the thymus were investigated to elucidate the physiologic events underlying this phenomenon. Two major effects were revealed: (i) CsA inhibits the development of mature single positive (CD4+8- or CD4-8+) TCR-alpha beta+ thymocytes without discernibly affecting CD4-8- TCR-gamma delta+ thymocytes and (ii) CsA interferes with the deletion of cells bearing self-reactive TCRs in the population of single positive thymocytes that do develop. This suggests a direct mechanism for CsA-induced autoimmunity and may have implications for the relative contribution of TCR-mediated signaling events in the development of the various T cell lineages.
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Citations
Cited by
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Starr, T. K., Jameson, S. C., & Hogquist, K. A. (2003) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141107 · Cited by 1,601
Acquisition of immunologic self-tolerance
Schwartz, R. H. (1989) · Cell · doi:10.1016/0092-8674(89)90044-5 · Cited by 477
Self-citationReproductive effort reduces specific immune response and parasite resistance
Nordling, D., Andersson, M., Zohari, S., & Lars, G. (1998) · Proceedings of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rspb.1998.0432 · Cited by 428
Kanakry, C. G., Ganguly, S., Zahurak, M., Bolaños-Meade, J., Thoburn, C., Perkins, B., Fuchs, E. J., Jones, R. J., Hess, A. D., & Luznik, L. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006960 · Cited by 357
POSITIVE VERSUS NEGATIVE SIGNALING BY LYMPHOCYTE ANTIGEN RECEPTORS
Healy, J. I., & Goodnow, C. C. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.645 · Cited by 316
Metadata
- Authors
- Jenkins, M., Schwartz, R., & Pardoll, D.
- Venue
- Science
- Published
- 1988-09-23
- Volume
- 241
- Issue
- 4873
- Pages
- 1655-1658
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2051349356
- Cited by
- 341
- References
- 0
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- closed
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- Jenkins, M., Schwartz, R., & Pardoll, D. (1988). Effects of cyclosporine A on T cell development and clonal deletion. Science. https://doi.org/10.1126/science.241.4873.1655
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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