Cyclosporine inhibits the expression of receptors for interleukin 2 and transferrin on mitogen-activated human T lymphocytes.
The effect of cyclosporine A (CsA) on the mitogen-induced expression of Interleukin 2 receptor (IL2R) and transferrin receptor (TR) was monitored using receptor-specific 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 microgram/ml). Titration experiments in the OKT3 system, the mitogen system most profoundly affected by CsA, revealed that CsA concentrations as low as 0.05 microgram/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.
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003524:Cyclosporins / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000502:physiology; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin / Q000187:drug effects* / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure*
D000911:Antibodies, Monoclonal; D003524:Cyclosporins; D007376:Interleukin-2; D008934:Mitogens; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D003208:Concanavalin A; D004247:DNA