ArticleJournal of virology2005
Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
155 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Correlation between COVID-19 and hepatitis B: A systematic review.World journal of gastroenterology · 2022Pooled it
- AFF3 maintains metabolic quiescence in naive CD8 T cells and prevents premature immune aging.JCI insight · 2026Article
- Sequential infection reprograms the immune landscape to shape future responses.bioRxiv : the preprint server for biology · 2026Article
- PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer.JCI insight · 2026Article
- Functional Type I and Type II interferon crosstalk restricts progenitor exhausted CD8 T cells through spatial exclusion and checkpoint enforcement.bioRxiv : the preprint server for biology · 2026Article
- COVID vaccination and post-infection cancer signals: Evaluating patterns and potential biological mechanisms.Oncotarget · 2026Review
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection.bioRxiv : the preprint server for biology · 2025Article
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- T Cell Exhaustion in Allergic Diseases and Allergen Immunotherapy: A Novel Biomarker?Current allergy and asthma reports · 2025Review
- Hepatitis B virus associated with severe acute respiratory syndrome coronavirus 2 infection: a case report.Journal of medical case reports · 2025Article
- The origin of autoimmune diseases: is there a role for ancestral HLA-II haplotypes in immune hyperactivity.Frontiers in immunology · 2025Review
- Stable characteristics of intrapopulation heterogeneity in virus-specific Th1 cells during chronic viral challenge infection.Frontiers in immunology · 2025Article
- Themis differentially regulates T follicular helper cell differentiation during early and late stages of chronic viral infection.Frontiers in immunology · 2025Article
- Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.PLoS biology · 2024Article
- Deciphering CD4Molecular carcinogenesis · 2024Review
- Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.Nature communications · 2024Article
- 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
- The role of CD4MedComm · 2023Review
- Molecular, metabolic, and functional CD4 T cell paralysis in the lymph node impedes tumor control.Cell reports · 2023Article
- Distribution modeling quantifies collective TScience advances · 2023Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Effective T-cell responses are critical to eradicate acute viral infections and prevent viral persistence. Emerging evidence indicates that robust, early CD4 T-cell responses are important in effectively sustaining CD8 T-cell activity. Herein, we illustrate that virus-specific CD4 T cells are functionally inactivated early during the transition into viral persistence and fail to produce effector cytokines (i.e., interleukin-2 and tumor necrosis factor alpha), thereby compromising an efficient and effective antiviral immune response. Mechanistically, the inactivation occurs at the cellular level and is not an active process maintained by regulatory T cells or antigen-presenting cells. Importantly, a small subpopulation of cells is able to resist inactivation and persist into the chronic phase of infection. However, the virus-specific CD4 T-cell population ultimately undergoes a second round of inactivation, and the cells that had retained functional capacity fail to respond to rechallenge in an acute time frame. Based on these results we propose a biological mechanism whereby early CD4 T-cell inactivation leads to a subsequent inability to sustain cytotoxic T-lymphocyte function, which in turn facilitates viral persistence. Moreover, these studies are likely relevant to chronic/persistent infections of humans (e.g., human immunodeficiency virus, hepatitis C virus, and hepatitis B virus) by providing evidence that a reservoir of virus-specific CD4 T cells can remain functional during chronic infection and represent a potential therapeutic target to stimulate the immune response and establish control of infection.
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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.