The dynamic changes of circulating invariant natural killer T cells during chronic hepatitis B virus infection
The dynamic changes of circulating invariant natural killer T cells during chronic hepatitis B virus infection
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慢性乙型肝炎病毒感染过程中循环不变自然杀伤T细胞的动态变化
DOI：
10.1007/s12072-015-9650-0
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发表时间：
2016-07-01
影响因子：
6.6
通讯作者：
Gao, Yue-Qiu
中科院分区：
文献类型：
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作者：
Li, Man;Zhou, Zhen-Hua;Gao, Yue-Qiu
恒定自然杀伤T细胞（iNKT）对B型肝炎病毒（HBV）感染的保护作用仍存在争议。为了阐明外周血iNKT细胞在慢性HBV感染中的作用，我们将60例慢性HBV感染患者分为免疫耐受期（HBV-IT）（n = 16）、免疫清除期（HBV-IC）（n = 19）和非活动性携带期（HBV-IA）（n = 25）。20名健康人作为健康对照。另21例HBeAg阳性患者口服恩替卡韦0.5mg/d，疗程6个月。通过流式细胞术检查循环iNKT细胞的百分比及其IFN-γ和IL-4表达水平。结果：与健康对照组相比，HBV-IT组iNKT细胞百分比降低，HBV-IC组和HBV-IA组iNKT细胞百分比升高;从HBV-IT期到HBV-IC和HBV-IA期，循环中产生IFN-γ的iNKT细胞逐渐增加，而产生IL-4的iNKT细胞逐渐减少。iNKT细胞的频率及其IFN-γ水平与病毒载量呈负相关。iNKT细胞表达IL-4的水平与病毒载量和血清ALT水平呈正相关。抗病毒治疗后，IFN-γ产生的iNKT细胞百分比增加，IL-4产生的iNKT细胞百分比下降，慢性HBV感染时，外周血iNKT细胞百分比及其细胞因子IFN-γ和IL-4的表达呈动态变化。IFN-γ和IL-4的表达水平与HBV清除和肝损伤相关。
The protective role of invariant natural killer T cells (iNKTs) against hepatitis B virus (HBV) infection remains controversial. We sought to clarify the role of peripheral iNKT cells during chronic HBV infection.Sixty patients with chronic HBV infection were categorized into an immune tolerance phase (HBV-IT) (n = 16), an immune clearance phase (HBV-IC) (n = 19) and an inactive carrier phase (HBV-IA) (n = 25). Twenty healthy individuals were enrolled as healthy controls. Another 21 HBeAg-positive patients were administrated with entecavir (0.5 mg/day) for 6 months. The percentages of circulating iNKT cells and their IFN-gamma and IL-4 expression levels were examined by flow cytometry. The relationships between serum HBV DNA, ALT levels, the percentages of iNKT cells, and their IFN-gamma and IL-4 levels were analyzed.Compared to healthy controls, the percentage of iNKT cells decreased in HBV-IT, but increased in HBV-IC and HBV-IA. Circulating IFN-gamma-producing iNKT cells gradually increased, whereas IL-4-producing iNKT cells gradually decreased from HBV-IT stage to HBV-IC and HBV-IA stages. The frequency of iNKT cells and their IFN-gamma levels were reversely correlated with viral load. The levels of IL-4 expressed by iNKT cells were positively correlated to viral load and the serum ALT levels. After anti-virus therapy, the percentage of IFN-gamma-producing iNKT cells increased while the percentage of IL-4-producing iNKT cells decreased.During chronic HBV infection, the percentages of peripheral iNKT cells and its cytokines expressions of IFN-gamma and IL-4 showed dynamic changes. The expression levels of IFN-gamma and IL-4 were correlated with the clearance of HBV and liver injury.