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Science 23 September 1988:
Vol. 241. no. 4873, pp. 1655 - 1658
DOI: 10.1126/science.3262237
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Articles

Science, Vol 241, Issue 4873, 1655-1658
Copyright © 1988 by American Association for the Advancement of Science

articles

Effects of cyclosporine A on T cell development and clonal deletion

MK Jenkins, RH Schwartz, and DM Pardoll

Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.

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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