Sidell N, Kummer U, Aframian D, Thierfelder S
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Cell Immunol. 1997 Aug 1;179(2):116-25. doi: 10.1006/cimm.1997.1157.
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.
维甲酸类化合物调节人T细胞白细胞介素-2受体（IL-2R）水平的能力可能在这些化合物的免疫调节作用中发挥着重要作用。作为研究这一现象的细胞系模型，我们检测了维甲酸（RA）对Hut78细胞中IL-2Rα和IL-2Rβ表达的影响，Hut78细胞是一种源自Sezary T细胞白血病的成熟T细胞系。我们的结果表明，当RA浓度从10^(-10)M开始时，这两种受体成分的表面表达和mRNA水平增加了4至20倍，在1μM RA时诱导作用最大。发现RA诱导的IL-2Rβ上调是以一种不依赖蛋白质合成的方式转录介导的；然而，在利用含有IL-2Rβ启动子所有目前已知调控元件的报告基因构建体进行的瞬时转染实验中，未能证明IL-2Rβ启动子的激活。RA对IL-2Rα/β的增强作用伴随着CD38、CD69、CD45RO和HLA-DR表达的上调，这些表面分子已知与T细胞活化有关。RA对原代人淋巴细胞产生的T母细胞也有类似的作用，这表明Hut78细胞系模型具有生理相关性。综上所述，我们的研究结果表明RA能够上调IL-2R表达并增强Hut78细胞的活化状态。RA对IL-2Rβ表达的显著增强能力似乎不是通过与IL-2Rβ启动子目前定义的区域相互作用介导的。
