ArticleAging cell2016
Characterization of age-associated exhausted CD8⁺ T cells defined by increased expression of Tim-3 and PD-1.
Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Impact of Age on the Efficacy of Immune Checkpoint Inhibitor-Based Combination Therapy for Non-small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Multivariate Computational Analysis of Gamma Delta T Cell Inhibitory Receptor Signatures Reveals the Divergence of Healthy and ART-Suppressed HIV+ Aging.Frontiers in immunology · 2018Trial
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- Article
- NF-κB-activated fibroblasts orchestrate inflammaging and emergence of pro-inflammatory granzyme KImmunity · 2026Article
- T cell senescence induced by DNMT1 deletion mediates cardiac transplant tolerance via altered CDKN1A methylation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Regulator of G protein signaling 10: a critical regulator of chronic systemic inflammation in parkinson's disease.Journal of neuroinflammation · 2026Review
- Intestinal T cells in aging: implications for gut barrier integrity and inflammaging.GeroScience · 2026Review
- T Cell Immunosenescence in Inflammatory Skin Diseases: Pathogenesis and Therapeutic Targets.Aging cell · 2026Review
- Human Immunodeficiency Virus-Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure.The Journal of infectious diseases · 2026Article
- The immunological fitness of NSCLC patients drives the response to anti-PD1-based immunotherapy regardless of age.Journal of translational medicine · 2026Article
- Modelling Immune Dynamics in Locally Advanced MSI-H/dMMR Colorectal Cancer with Neoadjuvant Pembrolizumab Treatment: From Differential Equations to an Agent-Based Framework.Bulletin of mathematical biology · 2026Article
- Regulators of CD8Nature reviews. Immunology · 2026Review
- Smoking accelerates immunosenescence in multiple sclerosis.Frontiers in immunology · 2026Review
- Conquering aging-related immunosenescence and tumor immune escape.Frontiers in immunology · 2026Review
- Immunosenescence modulates radiation-induced anti-tumor immunity: implications for personalized immuno-oncology.Frontiers in immunology · 2026Review
- Aging-induced hepatocyte CD44 drives IL6/STAT3 signaling and associates with impaired neighboring T cell function.bioRxiv : the preprint server for biology · 2025Article
- T Cell Exhaustion: Phenomenon, Diagnostic and Prognostic Significance, Age-Related Features, and Correction in Lung Cancer.Bulletin of experimental biology and medicine · 2025Article
- Age-stratified circulating immune signatures reveal non-invasive biomarkers for colorectal cancer detection.Immunity & ageing : I & A · 2025Article
- Fibroblast orchestration of inflammaging via NF-kB activation.bioRxiv : the preprint server for biology · 2025Article
33 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
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aging is accompanied by altered T-cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD-1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T-cell exhaustion and aging-associated immune dysfunction. In this study, we demonstrate that T-cell immunoglobulin mucin domain-3 (Tim-3), another exhaustion marker, is up-regulated on aged T cells, especially CD8(+) T cells. Tim-3-expressing cells also produced PD-1, but Tim-3(+) PD-1(+) CD8(+) T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim-3(-) PD-1(+) cells. Tim-3(+) PD-1(+) CD8(+) T cells showed more evident properties associated with exhaustion than Tim-3(-) PD-1(+) CD8(+) T cells: an exhaustion-related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL-10 and induced normal CD8(+) T cells to produce IL-10, which might contribute to immune dysregulation in aged mice. The generation of Tim-3-expressing CD8(+) T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8(+) T-cell population with age-associated exhaustion was distinguishable by its expression of Tim-3. These results provide clues for understanding the alterations that occur in T-cell populations with age and for improving dysfunctions related to the aging of the immune system.
Indexed as
Identifiers
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.