INTERLEUKIN-2 INDUCTION OF PORE-FORMING PROTEIN GENE-EXPRESSION IN HUMAN PERIPHERAL-BLOOD CD8+ T-CELLS
INTERLEUKIN-2 INDUCTION OF PORE-FORMING PROTEIN GENE-EXPRESSION IN HUMAN PERIPHERAL-BLOOD CD8+ T-CELLS
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DOI：
10.1084/jem.171.4.1269
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发表时间：
1990-04-01
影响因子：
15.3
通讯作者：
YOUNG, HA
中科院分区：
文献类型：
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作者：
SMYTH, MJ;ORTALDO, JR;YOUNG, HA
我们的研究分析了孔形成蛋白（PFP）mRNA表达在静息和刺激的人外周血CD 3-大颗粒淋巴细胞（LGL），CD 3 + T细胞，和他们的CD 4+或CD 8+亚群。刺激T细胞产生细胞毒性活性的信号（即，IL-2或OKT-3 mAb）导致T细胞中PFP mRNA的诱导。数据表明，在没有新的DNA或蛋白质合成的情况下，IL-2直接增加了T细胞的CD 8+亚群中的PFP mRNA。通过抗p75 IL-2受体mAb消除IL-2诱导的PFP mRNA表达和T细胞的细胞毒性潜力表明，CD 8 + T细胞上的少量p75 IL-2受体能够转导负责这些IL-2诱导效应的信号。使用OKT-3 mAb通过CD 3诱导T细胞PFP mRNA的速度较慢，但大于IL-2引起的速度;然而，PMA和离子霉素的组合绕过TCR/Cd 3复合物的交联，不能模拟T细胞中PFP mRNA水平的增加。第二信使系统在调节PFP mRNA表达中的作用仍有待确定。相反，在CD 3- LGL中观察到高组成性PFP mRNA表达，并且这些mRNA水平不能通过用IL-2刺激来增强。外周血T细胞和LGL的细胞毒性潜力诱导响应IL-2与IL-2诱导的PFP在这些细胞中的mRNA水平，并与PFP是参与细胞毒性淋巴细胞的效应功能的几个重要分子之一是一致的。
Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL-2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL-2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/Cd3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL-2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.