ArticleProceedings of the National Academy of Sciences of the United States of America2011
Antigen-specific CD4 T-cell help rescues exhausted CD8 T cells during chronic viral infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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.
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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
135 citing papers in PubMed, 192 citations in OpenAlex.
- The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.Journal of acquired immune deficiency syndromes (1999) · 2016Trial
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- Stepwise differentiation from precursor intermediates and distinct Th1 checkpoints promote CD4 Th1 cell differentiation during chronic viral infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Adaptive-like CAR-iPSC-CD4⁺ T cells outperform CD8⁺ counterparts in sustained ALL control.Inflammation and regeneration · 2026Article
- Immunosenescence promotes cancer development: from mechanisms to treatment strategies.Cell communication and signaling : CCS · 2025Review
- Low-avidity T cells drive endogenous tumor immunity in mice and humans.Nature immunology · 2025Article
- Themis differentially regulates T follicular helper cell differentiation during early and late stages of chronic viral infection.Frontiers in immunology · 2025Article
- The 41BB-agonist potentiates the therapeutic efficacy of a combined irreversible electroporation ablation treatment of lung cancer by promoting unexpected CD8Frontiers in immunology · 2025Article
- CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies.Frontiers in immunology · 2025Review
- Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.PLoS biology · 2024Article
- Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.International immunology · 2024Review
- Long-term outcome of natalizumab-associated progressive multifocal leukoencephalopathy in Austria: a nationwide retrospective study.Journal of neurology · 2024Article
- Abatacept increases T cell exhaustion in early RA individuals who carry HLA risk alleles.Frontiers in immunology · 2024Article
- Anti-CTLA-4 treatment suppresses hepatocellular carcinoma growth through Th1-mediated cell cycle arrest and apoptosis.PloS one · 2024Article
- Immune Checkpoints in Solid Organ Transplantation.Biology · 2023Review
- The Role of CD4 T Cell Help in CD8 T Cell Differentiation and Function During Chronic Infection and Cancer.Immune network · 2023Review
75 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
10 authors at 3 institutions in 1 country.
Funding
Abstract
CD4 T cells play a critical role in regulating CD8 T-cell responses during chronic viral infection. Several studies in animal models and humans have shown that the absence of CD4 T-cell help results in severe dysfunction of virus-specific CD8 T cells. However, whether function can be restored in already exhausted CD8 T cells by providing CD4 T-cell help at a later time remains unexplored. In this study, we used a mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Adoptive transfer of LCMV-specific CD4 T cells into chronically infected mice restored proliferation and cytokine production by exhausted virus-specific CD8 T cells and reduced viral burden. Although the transferred CD4 T cells were able to enhance function in exhausted CD8 T cells, these CD4 T cells expressed high levels of the programmed cell death (PD)-1 inhibitory receptor. Blockade of the PD-1 pathway increased the ability of transferred LCMV-specific CD4 T cells to produce effector cytokines, improved rescue of exhausted CD8 T cells, and resulted in a striking reduction in viral load. These results suggest that CD4 T-cell immunotherapy alone or in conjunction with blockade of inhibitory receptors may be a promising approach for treating CD8 T-cell dysfunction in chronic infections and cancer.
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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.