ArticleCellular & molecular immunology2016
Effective intrahepatic CD8+ T-cell immune responses are induced by low but not high numbers of antigen-expressing hepatocytes.
Article in Cellular & molecular immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- In vivo armed macrophages curb liver metastasis through tumor-reactive T-cell rejuvenation.Nature communications · 2025Article
- A novel, small anti-HBV compound reduces HBsAg and HBV-DNA by destabilizing HBV-RNA.Journal of gastroenterology · 2024Article
- Anti-CD122 antibody restores specific CD8Oncoimmunology · 2023Article
- In Vivo Bioluminescence Imaging of HBV Replicating Hepatocytes Allows for the Monitoring of Anti-Viral Immunity.Viruses · 2021Article
- Immunological exhaustion: How to make a disparate concept operational?PLoS pathogens · 2021Review
- Autoantigen presentation by splenic dendritic cells is required for RBC-specific autoimmunity.Transfusion · 2021Article
- Integrated Genomic Characterization of the Human Immunome in Cancer.Cancer research · 2020Article
- Article
- Review
- Efficacy of an Inhibitor of Hepatitis B Virus Expression in Combination With Entecavir and Interferon-α in Woodchucks Chronically Infected With Woodchuck Hepatitis Virus.Hepatology communications · 2020Article
- Priming of Antiviral CD8 T Cells without Effector Function by a Persistently Replicating Hepatitis C-Like Virus.Journal of virology · 2020Article
- Improved Functionality of Exhausted Intrahepatic CXCR5+ CD8+ T Cells Contributes to Chronic Antigen Clearance Upon Immunomodulation.Frontiers in immunology · 2020Article
- Targeting cardiac fibrosis with engineered T cells.Nature · 2019Article
- Synergy of therapeutic heterologous prime-boost hepatitis B vaccination with CpG-application to improve immune control of persistent HBV infection.Scientific reports · 2019Article
- Outcome of Antiviral Immunity in the Liver Is Shaped by the Level of Antigen Expressed in Infected Hepatocytes.Hepatology (Baltimore, Md.) · 2018Article
- Liver-Targeted Anti-HBV Single-Stranded Oligonucleotides with Locked Nucleic Acid Potently Reduce HBV Gene Expression In Vivo.Molecular therapy. Nucleic acids · 2018Article
- The Contribution of Non-Professional Antigen-Presenting Cells to Immunity and Tolerance in the Liver.Frontiers in immunology · 2018Review
- Cheating the Hunger Games; Mechanisms Controlling Clonal Diversity of CD8 Effector and Memory Populations.Frontiers in immunology · 2018Review
- TLR9-Mediated Conditioning of Liver Environment Is Essential for Successful Intrahepatic Immunotherapy and Effective Memory Recall.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- CpG-ODN Facilitates Effective Intratracheal Immunization and Recall of Memory against Neoantigen-Expressing Alveolar Cells.Frontiers in immunology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver infections with hepatotropic viruses, such as hepatitis B virus and hepatitis C virus are accompanied by viral persistence and immune failure. CD8+ T cells are crucial mediators of the intrahepatic antiviral immune response. Chronic infections of the liver and other organs correlate with T-cell exhaustion. It was previously suggested that high antigen load could result in T-cell exhaustion. We aimed at elucidating the impact of different intrahepatic antigen loads on the quality of CD8+ T-cell-mediated immunity by employing an infection-free transgenic mouse model expressing ovalbumin (Ova) as the target antigen. Adoptive transfer of OT-I cells induced a transient intrahepatic immune response toward both high and low Ova levels. However, antigen clearance was achieved only in mice expressing low antigen levels. In contrast, T cells exposed to high antigen levels underwent exhaustion and became depleted, causing antigen persistence. Moreover, when functional T cells were exposed to high intrahepatic antigen levels, a complete transition toward exhaustion was observed. Thus, this study shows that the antigen expression level in the liver correlates inversely with T-cell immunity in vivo and governs the efficiency of immune responses upon antigen presentation.
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Registered trials
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.