Control of biologically active interleukin 2 messenger RNA formation in induced human lymphocytes.

The regulation of human interleukin 2 (IL-2) mRNA production in induced normal lymphocytes was studied by following the expression of isolated mRNA in microinjected oocytes of Xenopus laevis. Mitogenic stimulation results in the appearance of greatly increased levels of IL-2 mRNA activity. This process requires de novo transcription. Induction is followed promptly by a shutoff of active IL-2 mRNA formation. This shutoff requires the synthesis of a protein repressor and can be prevented by cycloheximide, an inhibitor of translation. The presence of cycloheximide leads to extensive superinduction of IL-2, concomitant with an increase in active IL-2 mRNA formation up to 30-fold over normal levels. The repressor appears to be short-lived, as the addition of cycloheximide after shutoff leads to an immediate resumption of active IL-2 mRNA formation. The shutoff mechanism is restored rapidly upon removal of cycloheximide. The repressed state is readily reversed also by reinduction of the cells, even soon after shutoff has occurred, without a refractory period. The accumulated active IL-2 mRNA decays with a half-life of about 20 hr. The net result is the generation of a relatively short wave of IL-2 mRNA activity, demonstrating the tight control of IL-2 gene expression.