Kinkhabwala M, Sehajpal P, Skolnik E, Smith D, Sharma V K, Vlassara H, Cerami A, Suthanthiran M
Rogosin Institute, Department of Medicine, Cornell University Medical College, New York, New York 10021.
J Exp Med. 1990 Mar 1;171(3):941-6. doi: 10.1084/jem.171.3.941.
Expression of the pluripotent molecule TNF in a focused and antigen-restricted fashion might provide an advantage to the host organism. Given the central role of T cells in antigen-specific immunity, we examined whether activated T cells express TNF on their cell surface. FACS analysis of highly purified normal human T cells labeled with an anti-TNF mAb revealed that T cells express cell surface TNF when signaled with the synergistic combination of a calcium ionophore, ionomycin, and a protein kinase C activator, 12-o-tetradecanoyl phorbol acetate. Cell surface radioiodination studies of stimulated T cells demonstrated the presence of 26-kD transmembrane protein, a size predicted by TNF cDNA and different from that of the 17-kD secreted TNF molecule. The induced cell surface expression of TNF could be blocked with cyclosporine and/or methylprednisolone, and Northern analysis for TNF-specific transcripts revealed that this inhibitory effect occurs pretranslationally. Our demonstration for the first time that stimulated normal human T cells display cell surface TNF provides a mechanistic basis for the realization of effects of TNF in an antigen-specific fashion.
以聚焦且抗原受限的方式表达多能分子TNF可能对宿主生物体具有优势。鉴于T细胞在抗原特异性免疫中的核心作用，我们研究了活化的T细胞是否在其细胞表面表达TNF。用抗TNF单克隆抗体标记的高度纯化的正常人T细胞的流式细胞术分析表明，当用钙离子载体离子霉素和蛋白激酶C激活剂12-O-十四酰佛波醇乙酸酯的协同组合进行信号传导时，T细胞表达细胞表面TNF。刺激的T细胞的细胞表面放射性碘化研究证明存在26-kD跨膜蛋白，这是TNF cDNA预测的大小，不同于17-kD分泌型TNF分子的大小。TNF诱导的细胞表面表达可被环孢素和/或甲基强的松龙阻断，TNF特异性转录本的Northern分析表明这种抑制作用发生在翻译前。我们首次证明刺激的正常人T细胞显示细胞表面TNF，为以抗原特异性方式实现TNF的作用提供了机制基础。
