Hepatitis B envelope antigen increases Tregs by converting CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs
Hepatitis B envelope antigen increases Tregs by converting CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs
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DOI：
10.3892/etm.2020.9107
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发表时间：
2020-10-01
影响因子：
2.7
通讯作者：
Su, Chuan
中科院分区：
文献类型：
--
作者：
Tang, Rui;Lei, Zhigang;Su, Chuan
B型肝炎病毒（HBV）可在人类中建立终身慢性感染，导致肝硬化、肝衰竭和肝细胞癌。慢性B型肝炎（CH B）患者表现出较弱的病毒特异性免疫应答。调节性T细胞（TCLs）在调节CHB患者的免疫应答中起关键作用。B型肝炎包膜抗原（HBeAg）阳性的CH B患者外周血中THBG的百分比高于HBeAg阴性的CH B患者。然而，HBeAg是否以及如何操纵宿主免疫系统以增加THBe的数量仍有待阐明。本手稿描述了HBeAg在小鼠模型中的初步免疫学研究。使用免疫表位数据库共有结合预测确定HBeAg中多个潜在的CD 4（+）T细胞表位。结果表明，HBeAg处理可增加小鼠脾中THBe的数量。HBeAg介导的T细胞亚群升高是通过CD 4（+）CD 25（-）T细胞转化为CD 4（+）CD 25（+）Foxp 3（+）T细胞而发生的。此外，体外研究表明，HBeAg刺激小鼠脾细胞产生增加的转化生长因子-β，这是使HBeAg能够将T细胞转化为T细胞所必需的。本研究的结果可能为HBeAg对THBG的影响提供进一步的证据，并有助于开发新的基于HBeAg的CHB免疫治疗。
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 in vitro and in vivo. Furthermore, it was indicated that the HBeAg-mediated increase in Tregs occurred through the conversion of CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) Tregs. Additionally, in vitro study illustrated that HBeAg stimulated murine spleen cells to produce increased transforming growth factor-beta, 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.