INDUCTION OF IL-5 EXPRESSION BY IL-2 IS RESISTANT TO THE IMMUNOSUPPRESSIVE AGENTS CYCLOSPORINE-A AND RAPAMYCIN

T cell cytokine expression may be induced by the cytokine IL-2 or via the Ton complex. The comparative effects of cytokine- and Ton-mediated signalling on the induction of human IL-5 mRNA were examined. Cytokin e mRNA expression was analysed by RT-PCR in fresh peripheral blood mon onuclear cells (PBMC) from normal individuals and in populations of ac tivated T lymphocytes, derived from phytohaemagglutinin (PHA)-stimulat ed PBMC. rIL-2 induced IL-5 expression in PBMC, the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely abolished by the protein synthesis inhibitor cyclo heximide. rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5 expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml. Rapamycin (RAP) had no effect on rIL-2-st imulated IL-5 expression, but suppressed IL-5 expression induced by PH A. The inhibitory effect of RAP on PHA-induced IL-5 expression was mor e apparent at 12 and 24 h after stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP indicat es that the IL-2R and the TCR are associated with different pathways r egulating IL-5 expression.