IL-12依赖于TRAIL途径增强NK细胞对Jurkat细胞的杀伤功能

IL-12-induced expression of TRAIL enhances the cytotoxicity of NK cells against Jurkat cells

目的:探讨IL-12增强正常人NK细胞对Jurkat细胞杀伤功能的相关机制。方法:纯化正常人NK细胞,分为加或不加IL-12两个刺激组,通过基因芯片筛选差异基因,并通过流式细胞术在单个细胞水平检测相关杀伤分子的表达。结果:基因芯片系统结果显示IL-12刺激组和未刺激组相比,17种基因具有显著性差异(fold change≥10),其中5种基因上调,12种基因下调。在IL-12的刺激作用下,TRAIL的表达在CD56+CD16+和CD56-CD16+NK细胞上显著增加。同时,Jurkat细胞亦高表达TRAIL受体TRAIL-R2(DR5)。TRAIL中和抗体RIK-2可以阻断IL-12诱导的NK细胞对Jurkat细胞的杀伤功能。结论:TRAIL是IL-12增强正常人NK细胞对Jurkat细胞杀伤功能的主要途径之一。

AIM：To study the mechanism underlying the IL-12-induced cytotoxic function of NK cells to Jurkat cells.METHODS： NK cells from peripheral blood mononuclear cells（PBMCs） were purified by magnetic sorting and stimulated with or without IL-12.The expression of genes on IL-12-treated and non-IL-12-treated NK cells was analyzed by gene chips and the expression of cytolytic molecules was evaluated by flow cytometry.RESULTS： Seventeen genes were up-（5/17） or down-regulated（12/17） on IL-12-treated NK cells compared with non-IL-12-treated NK cells（fold change≥10）.IL-12-induced expression of TRAIL on NK cells mediated the cytotoxicity to Jurkat cells.The expression of TRAIL on subsets of CD56＋CD16＋ and CD56-CD16＋ NK cells significantly increased after the stimulation with IL-12 and Jurkat cells expressed high level of TRAIL receptor 2（TRAIL-R2）.Importantly,the neutralizing mAbs against TRAIL（RIK-2） significantly inhibited the cytotoxicity of NK cells induced by IL-12.CONCLUSION： The expression of TRAIL on human NK cells induced by IL-12 was one of the major mechanisms of cytotoxicity to Jurkat cells.