Virus-specific T cells are critical to mediating viral control; however, Hepatitis B virus (HBV)-specific T cells among chronic Hepatitis B (CHB) patients are functionally exhausted. The inability to consistently measure the ex vivo functionality of HBV-specific T cells has prevented meaningful analysis during antiviral events such as HBeAg seroconversion, hepatic flares, and HBsAg loss. We optimized the traditional IFN-γ ELISpot assay to measure total ex vivo HBV-specific T cell frequencies using CHB PBMCs stimulated with HBV overlapping peptide (OLP) pools. This was then further adapted to assess individual antigen specificity (core, envelop, polymerase, X) and multifunctional HBV-specific T cells using a 3-analyte FluoroSpot assay. This protocol encompasses two major components: (1) PBMC handling/stimulation and (2) assay plate preparation and spot development. By performing this assay, ex vivo CHB patient T cell responses could be assessed longitudinally during immunotherapy or other important clinical events.
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http://dx.doi.org/10.1007/978-1-0716-4027-2_20 | DOI Listing |
World J Gastrointest Oncol
January 2025
Institute of Liver Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China.
In this editorial, we comment on the article by Mu , published in the recent issue of the . We pay special attention to the immune tolerance mechanism caused by hepatitis B virus (HBV) infection, the pathogenesis of hepatocellular carcinoma (HCC), and the role of antiviral therapy in treating HCC related to HBV infection. HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways, as well as by inhibiting the immune functions of macrophages, natural killer cells and dendritic cells.
View Article and Find Full Text PDFJ Viral Hepat
February 2025
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Dendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74).
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Backgrounds And Aims: CD8+T cells are crucially associated with the fight against hepatitis B virus (HBV) infection. CD161 has been shown to express remarkably on HCV-specific CD8+T cells. However, the accurate function of CD161+CD8+T cells in HBV immunity or pathogenesis remains undetermined.
View Article and Find Full Text PDFHum Vaccin Immunother
December 2025
Department of General Practice, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
One of the key features of chronic hepatitis B virus (HBV) infection is the inability to mount sufficient and coordinated adaptive immune responses against HBV. Recent studies on HBV-specific B cells and antibody to hepatitis B surface antigen (anti-HBs) have shed light on their role in the pathogenesis of chronic hepatitis B (CHB). Anti-HBs is recognized as a protective immune marker, both for HBV infection clearance and following vaccination, and it is also considered an important indicator of functional cure for CHB.
View Article and Find Full Text PDFHepatology
December 2024
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Objective: Chronic HBV infection (CHB) exhausts HBV-specific T cells, develops epigenetic imprints that impair immune responses, and limits the effectiveness of immune checkpoint inhibitor (ICI) monotherapy, such as αPD-L1. This study aimed to determine whether the DNA methyltransferase inhibitor decitabine (DAC) could reverse these epigenetic imprints and enhance ICI efficacy in restoring HBV-specific T cell responses.
Methods: We investigated HBV-specific T cell responses by 10-day in vitro stimulation of peripheral blood mononuclear cells (PBMCs) from patients with CHB.
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