Immune response of Th17-associated cytokines by peripheral blood mononuclear cells from patients with chronic hepatitis C virus infection
Immune response of Th17-associated cytokines by peripheral blood mononuclear cells from patients with chronic hepatitis C virus infection
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DOI：
10.1016/j.cyto.2017.09.015
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发表时间：
2018-02-01
期刊：
影响因子：
3.8
通讯作者：
Sousa-Atta, Maria Luiza B.
中科院分区：
文献类型：
--
作者：
Cabral, Milena S.;Santos, Taciana P. S.;Sousa-Atta, Maria Luiza B.
丙型肝炎病毒（HCV）慢性感染导致严重的细胞免疫功能障碍。在这里，我们研究了未经治疗的HCV患者外周血单个核细胞（PBMC）的Th 17相关细胞因子的产生，在用干扰素-a加利巴韦林联合或不联合HCV蛋白酶抑制剂治疗12周后出现早期病毒学应答（EVR）的患者，以及对HCV治疗无应答的患者。用HCV核心抗原和非结构抗原刺激PBMC，用Milliplex MAP免疫测定法测定Th 17相关细胞因子的产生。来自未治疗和无应答患者的核心刺激的PBMC产生白细胞介素（IL）-17 A，并且仅在未治疗组中验证了响应于NS 3抗原的IL-17 A的剧烈产生。无应答患者在核心抗原刺激后也产生IL-17 F。IL-21的产生在三组患者中没有改变，而IL-17 E和IL-22未检测到。来自显示EVR的患者的细胞的Th 17细胞因子的产生是不显著的。IL-17 A和IL-17 F水平与丙氨酸氨基转移酶水平或病毒血症无关。然而，晚期纤维化与用核心抗原刺激的TO细胞中较高的IL-17 A产生相关。未经治疗的HCV患者和对抗病毒治疗无应答的患者在Th 17相关细胞因子的PBMC免疫应答方面存在差异。抗病毒治疗的早期病毒学应答显著降低了Th 17对HCV抗原的免疫应答。
Hepatitis C virus (HCV) chronic infection causes severe cellular immune dysfunction. Here, we investigated the production of Th17-associated cytokines by peripheral blood mononuclear cells (PBMCs) of untreated patients with HCV, patients presenting an early virologic response (EVR) after 12 weeks of treatment with interferon-a plus ribavirin with or without HCV protease inhibitors, and patients who were nonresponders to HCV therapy. PBMCs were stimulated with HCV core and nonstructural antigens, and the production of Th17-associated cytokines was measured with a Milliplex MAP immunoassay. Core-stimulated PBMCs from both untreated and nonresponder patients produced interleukin (IL)-17A, and vigorous production of IL-17A in response to NS3 antigen was only verified in the untreated group. Nonresponder patients also produced IL-17F after core antigen stimulation. IL-21 production was unaltered in the three groups of patients, whereas IL-17E and IL-22 were not detected. The production of Th17 cytokines by cells from patients showing an EVR was insignificant. IL-17A and IL-17F levels were not correlated with alanine aminotransferase levels or viremia. However, advanced fibrosis was associated with higher IL-17A production in TO cells stimulated with core antigen. Untreated patients with HCV and patients who were nonresponders to antiviral treatment differed in their PBMC immune responses of Th17-associated cytokines. The early virological response to antiviral treatment dramatically decreased Th17 immune responses to HCV antigens.