Pathogenic Interaction between Natural Killer (NK) and T cells in chronic Hepatitis B Virus Infection

乙型肝炎病毒（HBV）持续感染全世界超过4亿人。慢性（长期）感染可能导致严重并发症，包括严重肝病和肝癌，每年造成100多万人死亡。人体利用一些特殊的细胞类型来对抗病毒。对抗病毒的主要细胞类型，称为T细胞，在慢性感染中严重受损。在这项研究中，我们将研究另一种称为自然杀伤细胞（NK）的细胞杀死有益T细胞的能力。NK细胞已经被证明能够在病毒性肝炎中引起肝损伤，我们发现慢性乙型肝炎患者中NK细胞的数量增加。功能失调的NK细胞也可能攻击健康的T细胞，导致慢性疾病，而不是与之抗争。本研究的目的是确定可能的NK细胞介导的死亡途径，导致T细胞“衰竭”。我们将使用在知情同意的情况下，在HBV感染患者的常规临床护理中获得的血液和肝脏样本。阻断这些有害的死亡途径将增强免疫系统，从而改善病毒控制，预防慢性疾病和肝损伤。

Hepatitis B virus (HBV) persistently infects more than 400 million people worldwide. Chronic (longterm) infection carries a risk of serious complications including severe liver disease and liver cancer and is responsible for more than 1 million deaths per year. The body combats the virus using a number of specialised cell types. The main cell type fighting the virus, called the T cell, is severely impaired in chronic infection. In this study we will be looking at the ability of another type of cell called Natural Killer (NK) cell, to kill the beneficial T cells. NK cells have already been shown to be able to cause liver damage in viral hepatitis and we have found increased numbers in patients with chronic hepatitis B. Malfunctioning NK cells may also attack healthy T cells, causing chronic disease instead of fighting it. The purpose of this study is to identify the possible NK cell-mediated death pathways leading to T cell ‘exhaustion‘. We will use blood and liver samples obtained during routine clinical care of patients infected with HBV following informed consent. Blocking these harmful death pathways will boost the immune system leading to improved viral control and prevention of chronic disease and liver damage.