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.
Methods
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.
Results
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).
Conclusion
These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB.
Metabolic interventions improve HBV envelope-specific T-cell responses in patients with chronic hepatitis B
Authors
Yu-Long Fu Shuang-Nan Zhou Wei Hu Jing Li Ming-Ju Zhou Xiao-Yu Li You-Yuan Wang Peng Zhang Si-Yuan Chen Xing Fan Jin-Wen Song Yan-Mei Jiao Ruonan Xu Ji-Yuan Zhang Cheng Zhen Chun-Bao Zhou Jin-Hong Yuan Ming Shi Fu-Sheng Wang Chao Zhang
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