Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B

Author:

Wang Li‐Tzu12,Chen Yu‐Hong3,Cheng Yang4,Fan Hsiu‐Lung5,Chen Teng‐Wei5,Shih Yu‐Lueng3,Hsieh Tsai‐Yuan3,Huang Wen‐Yen6,Huang Wei‐Chen3

Affiliation:

1. School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology Taipei Medical University Taipei Taiwan

2. Ph.D. Program in Medical Biotechnology, College of Medical Science and Technology Taipei Medical University Taipei Taiwan

3. Department of Internal Medicine, Division of Gastroenterology, Tri‐Service General Hospital National Defense Medical Center Taipei Taiwan

4. Division of Infectious Disease & Immunology Institute of Biomedical Science, Academia Sinica Taipei Taiwan

5. Department of Surgery, Division of Organ Transplantation Surgery Tri‐Service General Hospital, National Defense Medical Center Taipei Taiwan

6. Department of Radiation Oncology, Tri‐Service General Hospital National Defense Medical Center Taipei Taiwan

Abstract

AbstractHepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.

Funder

Tri-Service General Hospital

Publisher

Wiley

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