Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Hepatol Int. 2023 Oct;17(5):1125-1138. doi: 10.1007/s12072-023-10490-4. Epub 2023 Mar 28.
Restoration of HBV-specific T cell immunity is a promising approach for the functional cure of chronic Hepatitis B (CHB), necessitating the development of valid assays to boost and monitor HBV-specific T cell responses in patients with CHB.
We analyzed hepatitis B virus (HBV) core- and envelope (env)-specific T cell responses using in vitro expanded peripheral blood mononuclear cells (PBMCs) from patients with CHB exhibiting different immunological phases, including immune tolerance (IT), immune activation (IA), inactive carrier (IC), and HBeAg-negative hepatitis (ENEG). Additionally, we evaluated the effects of metabolic interventions, including mitochondria-targeted antioxidants (MTA), polyphenolic compounds, and ACAT inhibitors (iACAT), on HBV-specific T-cell functionality.
We found that HBV core- and env-specific T cell responses were finely coordinated and more profound in IC and ENEG than in the IT and IA stages. HBV env-specific T cells were more dysfunctional but prone to respond to metabolic interventions using MTA, iACAT, and polyphenolic compounds than HBV core-specific T-cells. The responsiveness of HBV env-specific T cells to metabolic interventions can be predicted by the eosinophil (EO) count and the coefficient of variation of red blood cell distribution width (RDW-CV).
These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB.
恢复 HBV 特异性 T 细胞免疫是功能性治愈慢性乙型肝炎（CHB）的一种有前途的方法，这需要开发有效的检测方法来增强和监测 CHB 患者的 HBV 特异性 T 细胞反应。
我们使用来自表现出不同免疫阶段的 CHB 患者的体外扩增外周血单核细胞（PBMC）分析乙型肝炎病毒（HBV）核心和包膜（env）特异性 T 细胞反应，包括免疫耐受（IT）、免疫激活（IA）、非活动载体（IC）和 HBeAg 阴性肝炎（ENEG）。此外，我们评估了代谢干预措施，包括靶向线粒体的抗氧化剂（MTA）、多酚化合物和 ACAT 抑制剂（iACAT）对 HBV 特异性 T 细胞功能的影响。
我们发现 HBV 核心和 env 特异性 T 细胞反应在 IC 和 ENEG 中比在 IT 和 IA 阶段更加协调和深刻。HBV env 特异性 T 细胞功能障碍更严重，但比 HBV 核心特异性 T 细胞更容易对 MTA、iACAT 和多酚化合物等代谢干预产生反应。HBV env 特异性 T 细胞对代谢干预的反应性可以通过嗜酸性粒细胞（EO）计数和红细胞分布宽度变异系数（RDW-CV）来预测。
这些发现可能为代谢增强 HBV 特异性 T 细胞治疗 CHB 提供有价值的信息。
