Cerdan C, Martin Y, Courcoul M, Mawas C, Birg F, Olive D
Unit 119, National Institute of Health and Medical Research, Marseilles, France.
J Immunol. 1995 Feb 1;154(3):1007-13.
Costimulatory molecules such as CD28 are required for induction of T cell clonal expansion and for prevention of T cell unresponsiveness. In combination with either CD3 or CD2 triggering, CD28 was shown to enhance T cell proliferation, cytolytic activity, production of cytokines and especially of IL-2, and expression of the IL-2R alpha-chain (IL-2R alpha). We and others have demonstrated that the costimulatory effect of CD28 on both IL-2 and IL-2R alpha expression results from a coordinated transcriptional activation of their genes and transcript stabilization. We show here that the CD28 stimulation, together with CD2, leads to a prolonged up-regulation of the constitutive expression of the IL-2R beta-chain in human peripheral T cells. As for IL-2R alpha, the increase in IL-2R beta gene expression seems to result from both transcriptional activation and transcript stabilization. In addition, IL-2 differentially regulates its own receptors, as only expression of IL-2R alpha, but not of IL-2R beta, is largely inhibited, at both the mRNA and protein levels, by blocking IL-2R mAbs. We propose that the long lasting T cell proliferation mediated by the CD2 and CD28 costimulation is mainly the consequence of the high and prolonged expression of both the IL-2R alpha- and beta-chains.
共刺激分子如CD28是诱导T细胞克隆扩增和防止T细胞无反应性所必需的。与CD3或CD2触发相结合时，CD28可增强T细胞增殖、细胞溶解活性、细胞因子尤其是IL-2的产生以及IL-2Rα链（IL-2Rα）的表达。我们和其他人已经证明，CD28对IL-2和IL-2Rα表达的共刺激作用源于其基因的协同转录激活和转录本稳定。我们在此表明，CD28刺激与CD2一起，可导致人外周血T细胞中IL-2Rβ链组成性表达的长期上调。至于IL-2Rα，IL-2Rβ基因表达的增加似乎源于转录激活和转录本稳定。此外，IL-2对其自身受体有不同的调节作用，因为通过阻断IL-2R单克隆抗体，仅在mRNA和蛋白质水平上，IL-2Rα的表达受到很大抑制，而IL-2Rβ的表达不受影响。我们提出，由CD2和CD28共刺激介导的持久T细胞增殖主要是IL-2Rα链和β链高表达和长期表达的结果。
