Tang Rui, Lei Zhigang, Wang Xinpeng, Qi Qianqian, He Jingjing, Liu Dan, Wang Xiaoxian, Chen Xiaojun, Zhu Jifeng, Li Yalin, Zhou Sha, Su Chuan
State Key Laboratory of Reproductive Medicine, Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Center for Global Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Exp Ther Med. 2020 Oct;20(4):3679-3686. doi: 10.3892/etm.2020.9107. Epub 2020 Aug 6.
Hepatitis B virus (HBV) can establish a lifelong chronic infection in humans, leading to liver cirrhosis, liver failure and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) exhibit a weak virus-specific immune response. Regulatory T cells (Tregs) play a key role in regulating the immune response in patients with CHB. Patients with hepatitis B envelope antigen (HBeAg)-positive CHB harbored a higher percentage of Tregs in their peripheral blood than those with HBeAg-negative CHB. However, whether and how HBeAg manipulates the host immune system to increase the population of Tregs remains to be elucidated. The present manuscript describes a preliminary immunological study of HBeAg in a mouse model. Multiple potential CD4 T cell epitopes in HBeAg were identified using Immune Epitope Database consensus binding prediction. It was demonstrated that HBeAg treatment increased the numbers of Tregs in mouse spleens and . Furthermore, it was indicated that the HBeAg-mediated increase in Tregs occurred through the conversion of CD4CD25 T cells into CD4CD25Foxp3 Tregs. Additionally, study illustrated that HBeAg stimulated murine spleen cells to produce increased transforming growth factor-β, which is required to enable HBeAg to convert T cells into Tregs. The results of the present study may provide further evidence of the effect of HBeAg on Tregs and aid in the development of novel HBeAg-based immunotherapy for CHB.
乙型肝炎病毒（HBV）可在人体内建立终身慢性感染，导致肝硬化、肝衰竭和肝细胞癌。慢性乙型肝炎（CHB）患者表现出较弱的病毒特异性免疫反应。调节性T细胞（Tregs）在调节CHB患者的免疫反应中起关键作用。乙肝e抗原（HBeAg）阳性的CHB患者外周血中Tregs的比例高于HBeAg阴性的CHB患者。然而，HBeAg是否以及如何操纵宿主免疫系统以增加Tregs的数量仍有待阐明。本手稿描述了在小鼠模型中对HBeAg进行的初步免疫学研究。使用免疫表位数据库共识结合预测法鉴定了HBeAg中多个潜在的CD4 T细胞表位。结果表明，HBeAg处理增加了小鼠脾脏中Tregs的数量。此外，研究表明，HBeAg介导的Tregs增加是通过将CD4CD25 T细胞转化为CD4CD25Foxp3 Tregs实现的。另外，研究表明，HBeAg刺激小鼠脾细胞产生更多的转化生长因子-β，这是使HBeAg将T细胞转化为Tregs所必需的。本研究结果可能为HBeAg对Tregs的作用提供进一步证据，并有助于开发基于HBeAg的新型CHB免疫疗法。
