Trial reportThe Journal of clinical investigation2020
Hepatitis C virus-specific CD4+ T cell phenotype and function in different infection outcomes.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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
33 citing papers in PubMed, 43 citations in OpenAlex.
- Hijacking Host Communication: The Central Role of Extracellular Vesicles in Infectious Disease Pathogenesis.Cells · 2026Review
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- Vaccine Development T-cell (MHC-I) Epitopes Identification Against the Indian HCV Genotype: An Approach Based on Immunoinformatic.Molecular biotechnology · 2026Article
- CD96 marks a phenotypically distinct checkpoint-associated HCV-specific CD8+ T-cell subset featuring memory-associated states.Frontiers in immunology · 2026Article
- T cell dysfunction and metabolic disruption in chronic hepatitis C virus infection.Frontiers in immunology · 2026Review
- Unveiling the nexus between direct-acting antivirals in hepatitis C virus elimination and immune response.Clinical and experimental medicine · 2025Review
- Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025Review
- Activation-Induced Marker Assay to Identify and Isolate HCV-Specific T Cells for Single-Cell RNA-Seq Analysis.Viruses · 2024Article
- Like a Rolling Stone? A Review on Spontaneous Clearance of Hepatitis C Virus Infection.Viruses · 2024Review
- Exploring T-Cell Immunity to Hepatitis C Virus: Insights from Different Vaccine and Antigen Presentation Strategies.Vaccines · 2024Review
- Biomarkers in Detection of Hepatitis C Virus Infection.Pathogens (Basel, Switzerland) · 2024Review
- Tissue adaptation of CD4 T lymphocytes in homeostasis and cancer.Frontiers in immunology · 2024Article
- Immunological Monitoring in Hepatitis C Virus Controlled Human Infection Model.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Review
- Envelope virus-mimetic nanovaccines by hybridizing bioengineered cell membranes with bacterial vesicles.iScience · 2022Article
- Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer.Clinical and experimental immunology · 2022Article
- T cell responses during HBV and HCV infections: similar but not quite the same?Current opinion in virology · 2021Review
- Immune Activation Induces Telomeric DNA Damage and Promotes Short-Lived Effector T Cell Differentiation in Chronic HCV Infection.Hepatology (Baltimore, Md.) · 2021Article
- Towards a Systems Immunology Approach to Understanding Correlates of Protective Immunity against HCV.Viruses · 2021Review
- Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
CD4+ T cell failure is a hallmark of chronic hepatitis C virus (HCV) infection. However, the mechanisms underlying the impairment and loss of virus-specific CD4+ T cells in persisting HCV infection remain unclear. Here we examined HCV-specific CD4+ T cells longitudinally during acute infection with different infection outcomes. We found that HCV-specific CD4+ T cells are characterized by expression of a narrower range of T cell inhibitory receptors compared with CD8+ T cells, with initially high expression levels of PD-1 and CTLA-4 that were associated with negative regulation of proliferation in all patients, irrespective of outcome. In addition, HCV-specific CD4+ T cells were phenotypically similar during early resolving and persistent infection and secreted similar levels of cytokines. However, upon viral control, CD4+ T cells quickly downregulated inhibitory receptors and differentiated into long-lived memory cells. In contrast, persisting viremia continued to drive T cell activation and PD-1 and CTLA-4 expression, and blocked T cell differentiation, until the cells quickly disappeared from the circulation. Our data support an important and physiological role for inhibitory receptor-mediated regulation of CD4+ T cells in early HCV infection, irrespective of outcome, with persistent HCV viremia leading to sustained upregulation of PD-1 and CTLA-4.
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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.