Zheng Q, Zhu Y Y, Chen J, Ye Y B, Li J Y, Liu Y R, Hu M L, Zheng Y C, Jiang J J
Center for Liver Disease, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
Lab of Immunooncology, Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, China.
Clin Exp Immunol. 2015 Jun;180(3):499-508. doi: 10.1111/cei.12597. Epub 2015 Apr 12.
Emerging evidence indicates that natural killer (NK) cells may contribute to liver injury in patients with hepatitis B virus (HBV) infection. Because HBV infection progresses through various disease phases, the cytolytic profiles of peripheral and intrahepatic NK cells in HBV-infected patients remain to be defined. In this study, we comprehensively characterized intrahepatic and peripheral NK cells in a cohort of HBV-infected individuals, and investigated their impact on liver pathogenesis during chronic HBV infection. The study population included 34 immune-clearance (IC) patients, 36 immune-tolerant (IT) carriers and 10 healthy subjects. We found that the activity of peripheral NK cells from IC patients was functionally elevated compared to IT carriers and controls, and NK cell activation was indicated by an increased expression of CD69, CD107a, interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Further analysis showed that the increased activity of both peripheral and hepatic NK cells was correlated positively with liver injury, which was assessed by serum alanine aminotransferase levels (ALT) and the liver histological activity index (HAI). Interestingly, the frequency of peripheral NK cells was reduced in IC patients (especially those with higher HAI scores of 3-4), but there was a concomitant increase in hepatic NK cells. The functionally activated NK cells are enriched preferentially in the livers of IC patients and skew towards cytolytic activity that accelerates liver injury in chronic hepatitis B (CHB) patients.
新出现的证据表明，自然杀伤（NK）细胞可能在乙型肝炎病毒（HBV）感染患者的肝损伤中发挥作用。由于HBV感染会经历不同的疾病阶段，HBV感染患者外周血和肝内NK细胞的细胞溶解特征仍有待明确。在本研究中，我们全面描述了一组HBV感染个体的肝内和外周血NK细胞特征，并研究了它们在慢性HBV感染期间对肝脏发病机制的影响。研究人群包括34例免疫清除（IC）患者、36例免疫耐受（IT）携带者和10名健康受试者。我们发现，与IT携带者和对照组相比，IC患者外周血NK细胞的活性在功能上有所升高，NK细胞活化表现为CD69、CD107a、干扰素（IFN）-γ和肿瘤坏死因子（TNF）-α表达增加。进一步分析表明，外周血和肝内NK细胞活性的增加均与肝损伤呈正相关，肝损伤通过血清丙氨酸氨基转移酶水平（ALT）和肝脏组织学活性指数（HAI）进行评估。有趣的是，IC患者外周血NK细胞频率降低（尤其是HAI评分为3-4的患者），但肝内NK细胞数量随之增加。功能活化的NK细胞优先富集于IC患者的肝脏中，并偏向于细胞溶解活性，从而加速慢性乙型肝炎（CHB）患者的肝损伤。
