ArticleGut2020
TOX defines the degree of CD8+ T cell dysfunction in distinct phases of chronic HBV infection.
Article in Gut, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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Who cites it
52 citing papers in PubMed, 68 citations in OpenAlex.
- Immunotherapy for virus-related hepatocellular carcinoma: recent progress and future directions.Annals of medicine · 2026Review
- Viral persistence and immune dysfunction in chronic hepatitis B: Mechanisms of post-treatment antigen asynchrony.iScience · 2026Review
- Article
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- Nur77 Is Associated With Polyfunctional Properties in Virus-Specific Human CD8European journal of immunology · 2026Article
- TOX drives CD4Nature immunology · 2026Article
- Not so cold after all: tumor infiltrating CD8+ T cells in EBV-positive Burkitt lymphoma are quiescent, not exhausted.bioRxiv : the preprint server for biology · 2026Article
- From exhaustion to functional cure: frontiers in reversing HBV-specific T-cell immunity.Frontiers in immunology · 2026Review
- ScRNA-seq Identifies High CXCL8 Linked to Liver Fibrosis in HBeAg-negative Chronic Hepatitis B Patients With Low HBsAg.Gastro hep advances · 2026Article
- Review
- Research Progress on Mechanisms of Immune Tolerance Induced by Hepatitis B Surface Antigen in Chronic HBV Infection.Journal of immunology research · 2026Review
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Traditional Chinese Medicine in Chronic Hepatitis B: Integrating Antiviral Effects and Immune Modulation in the Context of T Cell Exhaustion.Drug design, development and therapy · 2026Review
- Immunometabolic Targets in CD8Liver cancer · 2025Review
- AAV-HBV mouse model replicates the intrahepatic immune landscape of chronic HBV patients at single-cell level.Frontiers in immunology · 2025Article
- The role of immune regulation in HBV infection and hepatocellular carcinogenesis.Frontiers in immunology · 2025Review
- Transcriptional reprogramming primes CD8+ T cells toward exhaustion in Myalgic encephalomyelitis/chronic fatigue syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Attenuated effector T cells are linked to control of chronic HBV infection.Nature immunology · 2024Article
- Harnessing CD8Clinical and translational medicine · 2024Review
- Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveChronic hepatitis B virus (HBV) infection is characterised by HBV-specific CD8+ T cell dysfunction that has been linked to Tcell exhaustion, a distinct differentiation programme associated with persisting antigen recognition. Recently, Thymocyte Selection-Associated High Mobility Group Box (TOX) was identified as master regulator of CD8+ T cell exhaustion. Here, we addressed the role of TOX in HBV-specific CD8+ T cell dysfunction associated with different clinical phases of infection.
designWe investigated TOX expression in HBV-specific CD8+ T cells from 53 HLA-A*01:01, HLA-A*11:01 and HLA-A*02:01 positive patients from different HBV infection phases and compared it to hepatitis C virus (HCV)-specific, cytomegalovirus (CMV)-specific, Epstein-Barr virus (EBV)-specific and influenza virus (FLU)-specific CD8+ T cells. Phenotypic and functional analyses of virus-specific CD8+ T cells were performed after peptide-loaded tetramer-enrichment and peptide-specific expansion.
resultsOur results show that TOX expression in HBV-specific CD8+ T cells is linked to chronic antigen stimulation, correlates with viral load and is associated with phenotypic and functional characteristics of T-cell exhaustion. In contrast, similar TOX expression in EBV-specific and CMV-specific CD8+ T cells is not linked to T-cell dysfunction suggesting different underlying programmes. TOX expression in HBV-specific CD8+ T cells is also affected by targeted antigens, for example, core versus polymerase. In HBV-specific CD8+ T cells, TOX expression is maintained after spontaneous or therapy-mediated viral control in chronic but not self-limiting acute HBV infection indicating a permanent molecular imprint after chronic but not temporary stimulation.
conclusionOur data highlight TOX as biomarker specific for dysfunctional virus-specific CD8+ T cells in the context of an actively persisting infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.