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.
Sidell
N
N
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Kummer
U
U
Aframian
D
D
Thierfelder
S
S
D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D015458:Leukemia, T-Cell / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000187:drug effects* / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014212:Tretinoin