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Cytokine Gene Expression Occurs More Rapidly in Stimulated Peripheral Blood Mononuclear Cells from Human Immunodeficiency Virus-Infected Persons

机译:细胞因子基因表达在人类免疫缺陷病毒感染者的刺激的外周血单个核细胞中发生得更快。

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Evaluation of cytokine gene expression following in vitro stimulation is one means of examining the dysregulation of the immune system in human immunodeficiency virus (HIV) infection. We have assessed differences in the immune status of non-HIV-infected (HIV?) and HIV-infected (HIV+) individuals by evaluating the kinetics of the expression of cytokine genes. We compared detailed time courses of cytokine mRNA expression in HIV? and HIV+ peripheral blood mononuclear cells (PBMC) and found that there is a significant shift (P < 0.01) for all cytokines examined (interleukin 2 [IL-2], IL-6, IL-10, gamma interferon, and tumor necrosis factor alpha [TNF-α]) to an earlier time of mean peak mRNA expression by HIV+ PBMC (between 4 and 8 h) compared to HIV? PBMC (8 h) in response to either phytohemagglutinin (PHA) or anti-CD3 stimulation. Additional studies showed that although PHA-stimulated HIV+ PBMC showed decreased median IL-2, IL-4, and TNF-α mRNA levels, they typically demonstrated more rapid kinetics (increased mean 4-h/24-h cytokine mRNA ratios), with significant differences for IL-4 (P < 0.05) and TNF-α (P < 0.005), compared to HIV? PBMC. The use of fresh or frozen cells gave comparable cytokine mRNA data; however, the secretion of some cytokine proteins (IL-2 receptor, IL-10, and TNF-α) appeared to be reduced in HIV+ PBMC that had been frozen and thawed. Our studies demonstrate that the kinetics of cytokine gene expression can reveal additional dysregulation of the immune system in HIV infection, suggesting that PBMC of HIV-infected persons exist in an activated state in vivo that permits them to express cytokine genes more rapidly than a normal PBMC.
机译:体外刺激后细胞因子基因表达的评估是检查人类免疫缺陷病毒(HIV)感染中免疫系统失调的一种手段。通过评估细胞因子基因表达的动力学,我们评估了非HIV感染(HIV?)和HIV感染(HIV +)个体的免疫状态差异。我们比较了HIV中细胞因子mRNA表达的详细时间过程。和HIV +外周血单个核细胞(PBMC),发现所有检查的细胞因子(白介素2 [IL-2],IL-6,IL-10, γ干扰素和肿瘤坏死因子α[TNF-α]),与HIV?PBMC相比,HIV + PBMC的平均峰值mRNA表达时间要早(4至8小时)。 PBMC(8小时)响应植物血凝素(PHA)或抗CD3刺激。进一步的研究表明,尽管PHA刺激的HIV + PBMC显示中值的IL-2,IL-4和TNF-αmRNA水平降低,但它们通常表现出更快的动力学特性(平均4小时/ 24小时细胞因子mRNA比率增加),与HIV相比,IL-4( P <0.05)和TNF-α( P <0.005)有显着差异。 PBMC。使用新鲜或冷冻细胞可得到类似的细胞因子mRNA数据。但是,已经冷冻和融化的HIV + PBMC中某些细胞因子蛋白(IL-2受体,IL-10和TNF-α)的分泌似乎减少了。我们的研究表明,细胞因子基因表达的动力学可以揭示HIV感染中免疫系统的其他失调,这表明HIV感染者的PBMC在体内处于激活状态,这使他们比正常PBMC更快地表达细胞因子基因。 。

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