Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls
Antigen-induced IL-17 response in the peripheral blood mononuclear cells (PBMC) of healthy controls
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DOI：
10.1046/j.1365-2249.2000.01328.x
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发表时间：
2000-10-01
影响因子：
4.6
通讯作者：
Kirkham, B
中科院分区：
文献类型：
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作者：
Lenarczyk, A;Helsloot, J;Kirkham, B
IL-17是在免疫系统中具有复杂和重要作用的T细胞细胞因子。已在类风湿性关节炎（RA）滑膜中检测到，并发现其在体外刺激促炎细胞因子IL-6、IL-8、肿瘤坏死因子-α（TNF-α）和粒细胞巨噬细胞集落刺激因子（GM-CSF）的产生。迄今为止，关于刺激IL-17产生的试剂的可用数据很少。因此，我们研究了体外IL-17对多种有丝分裂原和抗原的应答，并比较了IL-17对干扰素-γ（IFN-γ）、IL-4、IL-10和TNF-α的应答。在这项研究中，我们使用0型抗原破伤风圆环（TT）、1型抗原结核分枝杆菌PPD、潜在的2型黑麦草（RG）抗原（Lol I）和自身抗原SS.B（La）刺激健康对照的PBMC。使用半定量逆转录-聚合酶链反应和细胞因子蛋白测定使用特异性ELISA技术，而IL-17产生的T细胞的频率测定流式细胞术。促分裂原伴刀豆球蛋白A，植物血凝素和佛波醇肉豆蔻酸酯乙酸酯/离子霉素诱导IL-17的显着增加，最高水平产生的抗CD 3/抗CD 28刺激。抗原TT和PPD随时间显著增加IL-17 mRNA表达，但在蛋白质水平上没有这种效果。在抗原特异性（TT、SS.B）和非特异性T细胞克隆中也可检测到IL-17蛋白，但水平低于lFN-γ。IL-17的产生与1型细胞因子IFN-γ或TNF-α或2型细胞因子IL-4或IL-10在mRNA或蛋白质水平上均不相关。
IL-17 is a T cell cytokine with a complex and important role in the immune system. It has been detected in rheumatoid arthritis (RA) synovial membrane and found to stimulate the production of the proinflammatory cytokines IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and granulocyte macrophage colony-stimulating factor (GM-CSF) in vitro. To date, there are few data available on the agents that stimulate IL-17 production. We therefore investigated the in vitro IL-17 response to a variety of mitogens and antigens, and compared the IL-17 response to interferon-gamma (IFN-gamma), IL-4, IL-IO and TNF-alpha. In this study we used a type-0 antigen, tetanus toroid (TT), a type-1 antigen, PPD from Mycobacterium tuberculosis, a potential type-2 rye grass (RG) antigen (Lol I) and an autoantigen SS.B (La), to stimulate PBMC from healthy controls. Cytokine mRNA was measured using semiquantitative reverse transcriptase-polymerase chain reaction and cytokine protein measured using specific ELISA techniques, while the frequency of IL-17-producing T cells was determined by flow cytometry. The mitogens concanavalin A, phytohaemagglutinin and phorbol myristate acetate/ionomycin induced a significant increase in IL-17, with the highest levels being produced by antiCD3/anti-CD28 stimulation. The antigens TT and PPD significantly increased IL-17 mRNA expression over time, but failed to have such an effect at the protein level. IL-17 protein was also detectable in both antigen-specific (TT, SS.B) and non-specific T cell clones, but at levels lower than lFN-gamma. IL-17 production did not correlate with either the type-1 cytokine IFN-gamma or TNF-alpha or the type-2 cytokine IL-4 or IL-10 at either the mRNA or protein level.