ArticlePloS one2014
CD4+ T-cell help is required for effective CD8+ T cell-mediated resolution of acute viral hepatitis in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- An ICOSL-armed oncolytic adenovirus activates CD4BMC medicine · 2026Article
- 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
- Cytotoxic CD4Frontiers in immunology · 2023Review
- CD4Cells · 2021Review
- Lost in Translation: Lack of CD4 Expression due to a Novel Genetic Defect.The Journal of infectious diseases · 2021Article
- Designing the next-generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures.Clinical & translational immunology · 2021Review
- CD4BMC immunology · 2019Article
- The orphan nuclear receptor LRH-1/NR5a2 critically regulates T cell functions.Science advances · 2019Article
- Complete Multilineage CD4 Expression Defect Associated With Warts Due to an Inherited Homozygous CD4 Gene Mutation.Frontiers in immunology · 2019Article
- The -Frontiers in immunology · 2018Article
- Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4Frontiers in immunology · 2017Review
- CD28 family of receptors on T cells in chronic HBV infection: Expression characteristics, clinical significance and correlations with PD-1 blockade.Molecular medicine reports · 2016Article
- Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils.Scientific reports · 2016Article
- T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance.Cell death & disease · 2015Review
- Cerebrospinal fluid (CSF) CD8+ T-cells that express interferon-gamma contribute to HIV associated neurocognitive disorders (HAND).PloS one · 2015Article
- Regulation of T cell proliferation by JMJD6 and PDGF-BB during chronic hepatitis B infection.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic CD8+ T cells are essential for the control of viral liver infections, such as those caused by HBV or HCV. It is not entirely clear whether CD4+ T-cell help is necessary for establishing anti-viral CD8+ T cell responses that successfully control liver infection. To address the role of CD4+ T cells in acute viral hepatitis, we infected mice with Lymphocytic Choriomeningitis Virus (LCMV) of the strain WE; LCMV-WE causes acute hepatitis in mice and is cleared from the liver by CD8+ T cells within about two weeks. The role of CD4+ T-cell help was studied in CD4+ T cell-lymphopenic mice, which were either induced by genetic deficiency of the major histocompatibility (MHC) class II transactivator (CIITA) in CIITA-/- mice, or by antibody-mediated CD4+ cell depletion. We found that CD4+ T cell-lymphopenic mice developed protracted viral liver infection, which seemed to be a consequence of reduced virus-specific CD8+ T-cell numbers in the liver. Moreover, the anti-viral effector functions of the liver-infiltrating CD8+ T cells in response to stimulation with LCMV peptide, notably the IFN-γ production and degranulation capacity were impaired in CIITA-/- mice. The impaired CD8+ T-cell function in CIITA-/- mice was not associated with increased expression of the exhaustion marker PD-1. Our findings indicate that CD4+ T-cell help is required to establish an effective antiviral CD8+ T-cell response in the liver during acute viral infection. Insufficient virus control and protracted viral hepatitis may be consequences of impaired initial CD4+ T-cell help.
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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.