Cyclosporine Inhibits the Expression of Receptors for Interleukin 2 and Transferrin on Mitogen-Activated Human T Lymphocytes

Abstract

The effect of cyclosporine A (CsA) on the mitogeninduced expression of Interleukin 2 receptor (IL2R) and transferrin receptor (TR) was monitored using receptorspecific monoclonal antibodies and flow cytometry. For all mitogens tested (PHA, Con A, OKT3, and Leu 4), expression of IL2R and TR, as well as DNA synthesis (3H-thymidine incorporation), were significantly reduced in the presence of CsA (0.5 ug/ml). Titration experiments in the OKT3 system, the mitogen system most profoundly affected by CsA, revealed that CsA concentrations as low as 0.05 μ/ml inhibited IL2R and TR expression and DNA synthesis, and that changes in DNA synthesis reflected changes in IL2R and TR expression. The addition of exogenous IL2 partially abrogated the CsA-mediated inhibition of all three activation parameters (IL2R, TR, DNA synthesis) in response to PHA, OKT3, and Leu 4. In contrast, exogenous IL2 did not reverse CsA-mediated reductions in Con A-stimulated activation parameters. These findings indicate that CsA inhibits mitogen-induced expression of IL2R and TR, and for some mitogen systems, this inhibition appears, at least in part, to be secondary to decreased IL2 production.