UP-REGULATION BY RETINOIC ACID OF INTERLEUKIN-2-RECEPTOR MESSENGER-RNA IN HUMAN LYMPHOCYTES-T

It was previously demonstrated that retinoic acid (RA) can enhance the functional responses of human T lymphocytes by increasing surface IL-2Rα chain protein expression on proliferating T blasts, resulting in augmented IL-2-dependent growth. In the present study, we used IL-2-maintained lymphoblasts generated from human thymocytes to show that RA enhancement of IL-2Rα is accompanied by an increase in steady-state levels of IL-2Rα mRNA. This increase occurred within 1 hr after the addition of RA to the culture and was inhibited by the presence of the protein synthesis inhibitor cycloheximide. RA did not alter the stability of either IL-2Rα on the cell surface or IL-2Rα mRNA, suggesting regulation by RA at the level of transcription. This contention was supported by the demonstrated ability of RA to activate the IL-2Rα promoter in a chloramphenicol acetyltransferase plasmid construct that was transfected into the blast cells. In addition to inducing IL-2Rα expression. RA also increased the surface expression and mRNA levels of IL-2Rβ, the 75-kDa component of the IL-2 receptor that mediates IL-2 signal transduction. These new findings showing regulation by RA of both IL-2Rα and IL-2Rβ suggest multiple pathways by which this retinoid can modulate functional IL-2 receptors.