Ghosh P, Tan T H, Rice N R, Sica A, Young H A
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1696-700. doi: 10.1073/pnas.90.5.1696.
Optimal activation of T cells requires at least two signals. One signal can be delivered by the antigen-specific T-cell receptor, and the second signal is provided by the costimulatory molecule(s) delivered by the antigen-presenting cell. CD28 is a T-cell surface molecule and stimulation through this protein plays an important role in delivering the second activation signal. In this report, we show that in human peripheral blood T cells, CD28-mediated signal transduction involves the rel family proteins--c-Rel, p50, and p65. Treatment of peripheral blood T cells with phorbol 12-myristate 13-acetate (PMA) and anti-CD28 monoclonal antibody (mAb) results in augmentation of nuclear c-Rel, p50, and p65, and this augmentation can occur in the presence of the immunosuppressant cyclosporin A. It is also shown in this report that, in response to PMA/anti-CD28 mAb or anti-CD3/anti-CD28 mAb, c-Rel, p50, and p65 are associated with CD28-responsive element present in the promoter of the human interleukin 2 gene. The functional significance of c-Rel involvement in the CD28-responsive complex is demonstrated by transient transfection analysis, where cotransfection of c-Rel augments the level of expression of a chloramphenicol acetyltransferase reporter gene linked to the CD28-responsive element.
T细胞的最佳激活至少需要两个信号。一个信号可由抗原特异性T细胞受体传递，第二个信号由抗原呈递细胞传递的共刺激分子提供。CD28是一种T细胞表面分子，通过该蛋白的刺激在传递第二个激活信号中起重要作用。在本报告中，我们表明在人外周血T细胞中，CD28介导的信号转导涉及rel家族蛋白——c-Rel、p50和p65。用佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）和抗CD28单克隆抗体（mAb）处理外周血T细胞会导致核内c-Rel、p50和p65增加，并且这种增加可在免疫抑制剂环孢素A存在的情况下发生。本报告还表明，响应PMA/抗CD28 mAb或抗CD3/抗CD28 mAb时，c-Rel、p50和p65与人白细胞介素2基因启动子中存在的CD28反应元件相关。通过瞬时转染分析证明了c-Rel参与CD28反应复合物的功能意义，其中c-Rel的共转染增加了与CD28反应元件相连的氯霉素乙酰转移酶报告基因的表达水平。
