Metabolic interventions improve HBV envelope-specific T-cell responses in patients with chronic hepatitis B

Author:

Fu Yu-Long,Zhou Shuang-Nan,Hu Wei,Li Jing,Zhou Ming-Ju,Li Xiao-Yu,Wang You-Yuan,Zhang Peng,Chen Si-Yuan,Fan Xing,Song Jin-Wen,Jiao Yan-Mei,Xu Ruonan,Zhang Ji-Yuan,Zhen Cheng,Zhou Chun-Bao,Yuan Jin-Hong,Shi Ming,Wang Fu-ShengORCID,Zhang Chao

Abstract

Abstract Background 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. Graphical abstract

Funder

Innovative Research Group Project of the National Natural Science Foundation of China

Beijing Nova Program

Publisher

Springer Science and Business Media LLC

Subject

Hepatology

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