ArticleThe Journal of clinical investigation2014
Intrinsic TGF-β signaling promotes age-dependent CD8+ T cell polyfunctionality attrition.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Single-cell transcriptional responses of T cells during microsporidia infection.Communications biology · 2025Article
- The aging of the immune system and its implications for transplantation.GeroScience · 2023Review
- Immune Response to Microsporidia.Experientia supplementum (2012) · 2022Article
- Immunity to acute virus infections with advanced age.Current opinion in virology · 2021Review
- Innate and Adaptive Immune Responses Against Microsporidia Infection in Mammals.Frontiers in microbiology · 2020Review
- The twilight of immunity: emerging concepts in aging of the immune system.Nature immunology · 2018Review
- Cutting Edge: The Aging Immune System Reveals the Biological Impact of Direct Antigen Presentation on CD8 T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus.PLoS pathogens · 2016Article
- Blimp-1-mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis.The Journal of experimental medicine · 2016Article
- A Human Trypanosome Suppresses CD8+ T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4+ Foxp3+ T Cells.PLoS pathogens · 2016Article
- Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.British journal of cancer · 2016Article
- IL-21 Is Important for Induction of KLRG1+ Effector CD8 T Cells during Acute Intracellular Infection.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.PloS one · 2016Article
- Encephalitozoon intestinalis Inhibits Dendritic Cell Differentiation through an IL-6-Dependent Mechanism.Frontiers in cellular and infection microbiology · 2016Article
- Effector CD8 T cell immunity in microsporidial infection: a lone defense mechanism.Seminars in immunopathology · 2015Review
- Aging and uremia: Is there cellular and molecular crossover?World journal of nephrology · 2015Review
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 4 institutions in 2 countries.
Funding
Abstract
Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8+ T cell polyfunctionality, primarily due to CD8+ T cell-extrinsic deficits, and that reduced CD8+ T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8+ T cell survival and polyfunctionality were suppressed by highly elevated TGF-β1. Furthermore, TGF-β depletion reduced effector CD8+ T cell apoptosis in both young and aged mice and enhanced effector CD8+ T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-β signaling in CD8+ T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-β1 promote apoptosis of CD8+ effector T cells and high TGF-β1 levels associated with age result in both CD8+ T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-β levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-β represents an evolutionarily conserved negative regulator of the immune response in aging organisms.
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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.