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研究发现严重病毒性肝炎的细胞机制

By LabMedica International staff writers
Posted on 07 Mar 2018
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图片:T调节细胞(也称 Tregs或调节性T细胞)是抑制其它细胞免疫应答的关键细胞,设计目的是限制过多的反应,防止出现自身免疫。Tregs的特征是表达CD4+、CD25+和Foxp3+,同时缺乏CD127(图片蒙BioLegend公司惠赐)。
图片:T调节细胞(也称 Tregs或调节性T细胞)是抑制其它细胞免疫应答的关键细胞,设计目的是限制过多的反应,防止出现自身免疫。Tregs的特征是表达CD4+、CD25+和Foxp3+,同时缺乏CD127(图片蒙BioLegend公司惠赐)。
众所周知,病毒性肝炎患者的活化免疫细胞杀灭肝细胞,但是它的调控机制尚未得到揭示。调节性T细胞(Tregs)抑制其它免疫细胞的活化,因而对于免疫系统的动态平衡非常重要。

然而,最近的研究显示的结果恰恰相反,在发炎的情况下,调节性T细胞的免疫抑制功能弱化,细胞对此的反应是分泌炎性细胞因子。同时,甲型、乙型和丙型病毒性肝炎都没观察到这一现象。

韩国大田市韩国科学技术院的医学家们分析了韩国63名急性甲肝(AHA)患者住院时(有些人是在稍后的时间点)收集的血样以及19名健康献血者的血样。收集接受肝移植时爆发急性甲肝的患者的肝组织。从全血中分离外周血单核细胞(PBMC),从肝组织中分离出淋巴细胞,用流式细胞术分析。用抗CD3和抗CD28刺激后,根据免疫荧光水平测量Treg细胞产生的细胞因子(CD4+CD25+Foxp3+)。基于DNA甲基化模式确定Treg细胞的表观遗传稳定性。

科学家在急性甲肝患者体内发现了比对照者体内比例更高的CD4+CD25+Foxp3+ Treg细胞,且在用抗CD3和抗CD28 (11.2%比2.8%)刺激时产生肿瘤坏死因子(TNF)。DNA甲基化分析证实了Treg细胞的鉴定结果。产生TNF的Treg细胞具有辅助性T17细胞的特征,包括RAR相关孤儿受体γ (RORγt)的水平上升,这样有利于产生TNF。Treg细胞的抑制功能弱于对照者。急性甲肝患者血液中产TNF Treg细胞的频度与他们血清中丙氨酸转氨酶的水平有关。

该研究的论文首先发表于2017年12月8日的《肠胃病学》(Gastroenterology)杂志的网络版。作者总结说,急性甲肝患者的Treg细胞相较健康人的Treg细胞功能已有所改变。急性甲肝患者的Treg细胞产生的TNF水平更高,获得辅助性T17细胞的特征,且抑制活性降低。这些细胞的存在与急性甲肝患者的严重肝损伤有关。论文的资深作者Eui-Cheol Shin教授说:“这项对调节性T细胞的研究首次揭示了病毒性肝炎患者体内的肝细胞损伤。它的重要意义在于将来治疗病毒性肝炎时确定用哪些细胞和分子作为靶体。”

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