Trial reportPloS one2014
Inhibitory phenotype of HBV-specific CD4+ T-cells is characterized by high PD-1 expression but absent coregulation of multiple inhibitory molecules.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Pooled it
- Hyper-Expression of PD-1 Is Associated with the Levels of Exhausted and Dysfunctional Phenotypes of Circulating CD161Frontiers in immunology · 2018Trial
- A Distinct Immune Signature Characterizes Cirrhosis in Ethiopian Individuals With Chronic HBV Infection.Alimentary pharmacology & therapeutics · 2026Article
- Bulk and Single-Cell Transcriptomes Reveal Exhausted Signature in Prognosis of Hepatocellular Carcinoma.Genes · 2025Article
- AAV-HBV mouse model replicates the intrahepatic immune landscape of chronic HBV patients at single-cell level.Frontiers in immunology · 2025Article
- Efficacy and safety of PD-1/PD-L1 inhibitors combined with tyrosine kinase inhibitors as first-line treatment for hepatocellular carcinoma: a meta-analysis and trial sequential analysis of randomized controlled trials.Frontiers in pharmacology · 2025Article
- Nanoengineered-based delivery systems to modulate CD4Frontiers in pharmacology · 2025Review
- Insights into Immune Exhaustion in Chronic Hepatitis B: A Review of Checkpoint Receptor Expression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Single-cell RNA-sequencing of virus-specific cellular immune responses in chronic hepatitis B patients.Scientific data · 2024Article
- Glutaminolysis of CD4Journal of inflammation research · 2024Review
- Dysfunction and regulatory interplay of T and B cells in chronic hepatitis B: immunotherapy and emerging antiviral strategies.Frontiers in cellular and infection microbiology · 2024Review
- Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation.Frontiers in immunology · 2023Review
- Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus.International journal of molecular sciences · 2022Review
- Advances in Immunotherapy for Hepatitis B.Pathogens (Basel, Switzerland) · 2022Review
- A Systematic Review of T Cell Epitopes Defined from the Proteome of Hepatitis B Virus.Vaccines · 2022Review
- Immunomodulatory regulator blockade in a viral exacerbation model of severe asthma.Frontiers in immunology · 2022Article
- TIGIT marks exhausted T cells and serves as a target for immune restoration in patients with chronic HBV infection.American journal of translational research · 2022Article
- Characterization of a library of 20 HBV-specific MHC class II-restricted T cell receptors.Molecular therapy. Methods & clinical development · 2021Article
- T cell responses during HBV and HCV infections: similar but not quite the same?Current opinion in virology · 2021Review
- CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT-cell exhaustion seems to play a critical role in CD8+ T-cell dysfunction during chronic viral infections. However, up to now little is known about the mechanisms underlying CD4+ T-cell dysfunction during chronic hepatitis B virus (CHB) infection and the role of inhibitory molecules such as programmed death 1 (PD-1) for CD4+ T-cell failure.
methodsThe expression of multiple inhibitory molecules such as PD-1, CTLA-4, TIM-3, CD244, KLRG1 and markers defining the grade of T-cell differentiation as CCR7, CD45RA, CD57 and CD127 were analyzed on virus-specific CD4+ T-cells from peripheral blood using a newly established DRB1*01-restricted MHC class II Tetramer. Effects of in vitro PD-L1/2 blockade were defined by investigating changes in CD4+ T-cell proliferation and cytokine production.
resultsCD4+ T-cell responses during chronic HBV infection was characterized by reduced Tetramer+CD4+ T-cell frequencies, effector memory phenotype, sustained PD-1 but low levels of CTLA-4, TIM-3, KLRG1 and CD244 expression. PD-1 blockade revealed individualized patterns of in vitro responsiveness with partly increased IFN-γ, IL-2 and TNF-α secretion as well as enhanced CD4+ T-cell expansion almost in treated patients with viral control.
conclusionHBV-specific CD4+ T-cells are reliably detectable during different courses of HBV infection by MHC class II Tetramer technology. CD4+ T-cell dysfunction during chronic HBV is basically linked to strong PD-1 upregulation but absent coregulation of multiple inhibitory receptors. PD-L1/2 neutralization partly leads to enhanced CD4+ T-cell functionality with heterogeneous patterns of CD4+ T-cell rejunivation.
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What OpenQuestion holds
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.