Geist L J, Monick M M, Stinski M F, Hunninghake G W
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
J Clin Invest. 1992 Nov;90(5):2136-40. doi: 10.1172/JCI116099.
The use of cyclosporin A (CsA) as an immunosuppressive agent has markedly improved the clinical outcome in solid organ transplantation. However, posttransplantation infection remains a significant problem and may contribute to subsequent organ rejection. In this study the effect of cytomegalovirus (CMV) immediate early (IE) gene products on interleukin 2 (IL-2) gene transcription in the absence and presence of CsA was investigated using a transient transfection system. Jurkat T cells were transfected with plasmids expressing the CMV IE gene products or with a control plasmid. The presence of the CMV IE2 gene product abolished the inhibitory effect of CsA on IL-2 promoter activation and gene transcription. This effect was noted regardless of the time of CsA addition relative to the time of stimulation and was independent of CsA concentration. CsA had no effect on the CMV or the IL-2 receptor promoters. These studies suggest that the CMV IE gene products may play a role in graft rejection after solid organ transplantation.
环孢素A(CsA)作为一种免疫抑制剂的使用显著改善了实体器官移植的临床结果。然而,移植后感染仍然是一个重大问题,并且可能导致随后的器官排斥反应。在本研究中,使用瞬时转染系统研究了巨细胞病毒(CMV)立即早期(IE)基因产物在有无CsA情况下对白细胞介素2(IL-2)基因转录的影响。用表达CMV IE基因产物的质粒或对照质粒转染Jurkat T细胞。CMV IE2基因产物的存在消除了CsA对IL-2启动子激活和基因转录的抑制作用。无论CsA相对于刺激时间的添加时间如何,均观察到这种效应,并且与CsA浓度无关。CsA对CMV或IL-2受体启动子没有影响。这些研究表明,CMV IE基因产物可能在实体器官移植后的移植物排斥中起作用。