Retinoid regulation of interleukin-2 receptors on human T-cells.

The ability of retinoids to regulate interleukin-2 receptor (IL-2R) levels on human T-cells may play a fundamental role in the immunomodulating effects of these compounds. As a cell line model for studying this phenomenon, we tested the effects of retinoic acid (RA) on the expression of IL-2Ralpha and IL-2Rbeta in Hut78 cells, a mature T-cell line derived from a Sezary T-cell leukemia. Our results demonstrated 4- to 20-fold increases in the surface expression and mRNA levels of both of these receptor components at RA concentrations starting at 10(-10) M with maximal induction at 1 microM RA. RA-induced upregulation of IL-2Rbeta was found to be transcriptionally mediated in a protein-synthesis-independent fashion; however, activation of the IL-2Rbeta promoter could not be demonstrated in transient transfection experiments utilizing reporter gene constructs containing all currently known regulatory elements of the IL-2Rbeta promoter. Enhancement of IL-2Ralpha/beta by RA was accompanied by upregulation of the expression of CD38, CD69, CD45RO, and HLA-DR, surface molecules known to be associated with T-cell activation. Parallel effects were induced by RA on T-blasts generated from primary human lymphocytes suggesting the physiologic relevance of the Hut78 cell line model. Taken together, our findings demonstrate the ability of RA to upregulate IL-2R expression and enhance the activation state of Hut78 cells. The dramatic enhancing ability of RA on IL-2Rbeta expression does not appear to be mediated through interaction with currently defined regions of the IL-2Rbeta promoter.