ArticleJournal of immunology (Baltimore, Md. : 1950)2009
CCR5 expression levels influence NFAT translocation, IL-2 production, and subsequent signaling events during T lymphocyte activation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Association of the CCR5 gene with juvenile idiopathic arthritis.Genes and immunity · 2010Pooled it
- Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial.PloS one · 2015Trial
- Effect of maraviroc intensification on HIV-1-specific T cell immunity in recently HIV-1-infected individuals.PloS one · 2014Trial
- CCR5 antagonism impacts vaccination response and immune profile in HIV-1 infection.Molecular medicine (Cambridge, Mass.) · 2012Trial
- A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256.The Journal of infectious diseases · 2012Trial
- CCR5Δ32 polymorphism is associated with increased central memory CD4+ T cells in virologically suppressed people living with HIV on antiretroviral therapy.Medical microbiology and immunology · 2026Article
- CCL5/RANTES signaling in inflammation dysregulation after mild traumatic brain injury.Journal of biomedical science · 2026Article
- CCR5 + T cells as a potential biomarker for primary Sjögren's disease based on bioinformatics analysis.Clinical rheumatology · 2025Article
- VI-VS: calibrated identification of feature dependencies in single-cell multiomics.Genome biology · 2024Article
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- Article
- Multi-omics in HIV: searching insights to understand immunological non-response in PLHIV.Frontiers in immunology · 2023Review
- People with HIV have higher percentages of circulating CCR5+ CD8+ T cells and lower percentages of CCR5+ regulatory T cells.Scientific reports · 2022Article
- LPA suppresses T cell function by altering the cytoskeleton and disrupting immune synapse formation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Generation of SIV-resistant T cells and macrophages from nonhuman primate induced pluripotent stem cells with edited CCR5 locus.Stem cell reports · 2022Article
- Natural killer cells induce HIV-1 latency reversal after treatment with pan-caspase inhibitors.Frontiers in immunology · 2022Article
- Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.Frontiers in immunology · 2021Review
- Reduced CCR5 Expression and Immune Quiescence in Black South African HIV-1 Controllers.Frontiers in immunology · 2021Article
- The Chemokine Receptor CCR5 Links Memory CD4Frontiers in immunology · 2021Article
- miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Ligands of CCR5, the major coreceptor of HIV-1, costimulate T lymphocyte activation. However, the full impact of CCR5 expression on T cell responses remains unknown. Here, we show that compared with CCR5(+/+), T cells from CCR5(-/-) mice secrete lower amounts of IL-2, and a similar phenotype is observed in humans who lack CCR5 expression (CCR5-Delta32/Delta32 homozygotes) as well as after Ab-mediated blockade of CCR5 in human T cells genetically intact for CCR5 expression. Conversely, overexpression of CCR5 in human T cells results in enhanced IL-2 production. CCR5 surface levels correlate positively with IL-2 protein and mRNA abundance, suggesting that CCR5 affects IL-2 gene regulation. Signaling via CCR5 resulted in NFAT transactivation in T cells that was blocked by Abs against CCR5 agonists, suggesting a link between CCR5 and downstream pathways that influence IL-2 expression. Furthermore, murine T cells lacking CCR5 had reduced levels of intranuclear NFAT following activation. Accordingly, CCR5 expression also promoted IL-2-dependent events, including CD25 expression, STAT5 phosphorylation, and T cell proliferation. We therefore suggest that by influencing a NFAT-mediated pathway that regulates IL-2 production and IL-2-dependent events, CCR5 may play a critical role in T cell responses. In accord with our prior inferences from genetic-epidemiologic studies, such CCR5-dependent responses might constitute a viral entry-independent mechanism by which CCR5 may influence HIV-AIDS pathogenesis.
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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.