ArticleProceedings of the National Academy of Sciences of the United States of America2010
Role of antigen persistence and dose for CD4+ T-cell exhaustion and recovery.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 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
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Pooled it
- Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Trial
- Peripheral immune landscape in pancreatic ductal adenocarcinoma reveals expansion of effector states with disease progression.iScience · 2026Article
- Transient loss of KLF2 expression is essential for CD8 effector T cell expansion.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- A pain from the nose to the head: neurological commitment during long COVID.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Cell-intrinsic CD4 T cell tolerance: a new frontier in therapy?Trends in immunology · 2025Review
- Increased CD8Immunology · 2025Article
- High antigen burden drives CD8+ T cell dysfunction in a mouse model of chronic hepatitis B virus infection.Journal of virology · 2025Article
- Identification of Shared Diagnostic Biomarkers LCN2 and DUOX2 for Inflammatory Bowel Disease and Cholangiocarcinoma Through Integrative Bioinformatics and Machine Learning.Journal of inflammation research · 2025Article
- Immune Checkpoint Molecules as Biomarkers ofbioRxiv : the preprint server for biology · 2024Article
- Advancing immunotherapy using biomaterials to control tissue, cellular, and molecular level immune signaling in skin.Advanced drug delivery reviews · 2024Review
- Promoter methylation and increased expression of PD-L1 in patients with active tuberculosis.Microbial cell (Graz, Austria) · 2024Article
- Epitope-based precision immunotherapy of Type 1 diabetes.Human vaccines & immunotherapeutics · 2023Article
- Exploiting Unique Features of Microneedles to Modulate Immunity.Advanced materials (Deerfield Beach, Fla.) · 2023Review
- Phosphatidylserine-positive extracellular vesicles boost effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Employing T-Cell Memory to Effectively Target SARS-CoV-2.Pathogens (Basel, Switzerland) · 2023Review
- Genetically engineered CD80-pMHC-harboring extracellular vesicles for antigen-specific CD4Frontiers in bioengineering and biotechnology · 2023Article
- Exhaustion and over-activation of immune cells in COVID-19: Challenges and therapeutic opportunities.Clinical immunology (Orlando, Fla.) · 2022Review
- Article
- Tumour burden and efficacy of immune-checkpoint inhibitors.Nature reviews. Clinical oncology · 2022Review
32 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
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is currently not understood how some chronic infections exhaust antigen-specific T cells over time and which pathogen components contribute to exhaustion. Here, we dissected the behavior of primed CD4(+) T cells exposed to persistent antigen using an inducible transgenic mouse system that allowed us to control antigen presentation as the only experimental variable, independent of the persistent inflammation and disease progression that complicate infectious models. Moreover, this system restricted antigen presentation to dendritic cells (DCs) and avoided confounding B, CD8(+) T, or innate cell responses. When antigen presentation was extended beyond the expansion phase, primed CD4(+) T cells survived, but exhibited reduced memory functionality in terms of their proliferative capacity and cytokine expression potential. The effect was antigen dose and time dependent, not associated with increased PD-1 expression or reduced calcium influx, but impaired Jun phosphorylation in response to TCR engagement. Upon antigen removal, the cells regained the ability to proliferate, but remained unable to produce high levels of IL-2 and TNF-α. These data show that persistent antigen by itself rapidly induces a dysfunctional state in CD4(+) T cells that is only partially reversible upon antigen removal. These findings have implications for vaccine optimization and for the possible reinvigoration of CD4(+) T cells during chronic 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.