Effects of cyclosporine A on T cell development and clonal deletion

Marc K. Jenkins, Ronald H. Schwartz, Drew M. Pardoll

Research output: Contribution to journalArticle

331 Scopus citations

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-αβ+ thymocytes without discernibly affecting CD4-8- TCR-γδ+ 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.

Original languageEnglish (US)
Pages (from-to)1655-1658
Number of pages4
JournalScience
Volume241
Issue number4873
DOIs
StatePublished - Jan 1 1988

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