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白细胞介素-7对细胞毒性淋巴细胞的调节作用:成孔蛋白基因表达、γ干扰素产生及人外周血淋巴细胞亚群的细胞毒性

IL-7 regulation of cytotoxic lymphocytes: pore-forming protein gene expression, interferon-gamma production, and cytotoxicity of human peripheral blood lymphocytes subsets.

作者信息

Smyth M J, Norihisa Y, Gerard J R, Young H A, Ortaldo J R

机构信息

Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702-1201.

出版信息

Cell Immunol. 1991 Dec;138(2):390-403. doi: 10.1016/0008-8749(91)90163-6.

DOI:10.1016/0008-8749(91)90163-6
PMID:1834347
Abstract

The effects of IL-7 on the generation of cytolytic human peripheral blood lymphocytes (PBL) were investigated. Induction of T-cell pore-forming protein (PFP) mRNA and cytotoxic potential by IL-7 was both slow and minor compared with that observed in IL-2-cultured T cells. IL-7 and suboptimal doses of IL-2 (10 U/ml) were found to costimulate PFP mRNA expression and cytotoxic potential in T cells. Clearly, however, both IL-7 and IL-2/IL-7 induced the PFP gene expression and cytotoxic potential of CD8+ T cells and not CD4+ T cells. In addition, neither monoclonal antibodies (mAb) to the p55 or p75 IL-2-receptor subunits had any effect upon IL-7 induction of CD8+ T-cell cytotoxicity, indicating that IL-7 induction of cytotoxic CD8+ T cells was IL-2 independent. IL-7 induction of CD3- large granular lymphocyte (LGL) and PB gamma delta T-cell cytotoxicity was also delayed and reduced compared with that effected by IL-2. IL-7 (10 or 1000 U/ml, 72 hr) enhanced the NK and LAK cytotoxic of LGL and PB gamma delta T cells. By contrast IL-7 or IL-2 augmented the redirected cytotoxic potential of PB gamma delta T cells, but not that of LGL, and neither lymphokine had any effect on constitutive PFP mRNA expression in either lymphocyte subset. In addition, IL-7 induction of LGL IFN-gamma production was weak and delayed compared with that effected by IL-2 and neither IL-2 nor IL-7 stimulated IFN-gamma production in PB gamma delta T cells. Therefore, overall the effects of IL-2 and IL-7 on various cytotoxic human PBL were qualitatively similar, but quantitatively and kinetically different.

摘要

研究了白细胞介素-7(IL-7)对人细胞毒性外周血淋巴细胞(PBL)生成的影响。与在白细胞介素-2(IL-2)培养的T细胞中观察到的情况相比,IL-7诱导T细胞穿孔素(PFP)mRNA和细胞毒性潜力的过程既缓慢又微弱。发现IL-7和次优剂量的IL-2(10 U/ml)可共刺激T细胞中PFP mRNA表达和细胞毒性潜力。然而,很明显,IL-7和IL-2/IL-7均诱导CD8⁺T细胞而非CD4⁺T细胞的PFP基因表达和细胞毒性潜力。此外,针对IL-2受体亚基p55或p75的单克隆抗体(mAb)对IL-7诱导的CD8⁺T细胞细胞毒性均无任何影响,这表明IL-7诱导细胞毒性CD8⁺T细胞是不依赖IL-2的。与IL-2相比,IL-7诱导CD3⁻大颗粒淋巴细胞(LGL)和外周血γδT细胞的细胞毒性也出现延迟且降低。IL-7(10或1000 U/ml,72小时)增强了LGL和外周血γδT细胞的自然杀伤(NK)和淋巴因子激活的杀伤(LAK)细胞毒性。相比之下,IL-7或IL-2增强了外周血γδT细胞的重定向细胞毒性潜力,但对LGL则无此作用,并且这两种淋巴因子对任一淋巴细胞亚群中组成性PFP mRNA表达均无任何影响。此外,与IL-2相比,IL-7诱导LGL产生γ干扰素(IFN-γ)的作用较弱且延迟,并且IL-2和IL-7均未刺激外周血γδT细胞产生IFN-γ。因此,总体而言,IL-2和IL-7对各种人细胞毒性PBL的作用在性质上相似,但在数量和动力学方面存在差异。

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