ArticleRejuvenation research2008
Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling.
Article in Rejuvenation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 43 citations in OpenAlex.
- Causal Link of Seven Trace Elements and Eight Nutrients With Meningioma: A Bidirectional Two-Sample Mendelian Randomization Analysis.Brain and behavior · 2025Article
- Zinc-mediated dynamics of CD4/CD8α co-receptors and Lck kinase: implications for zinc homeostasis, immune response, and biotechnological innovations.Metallomics : integrated biometal science · 2025Review
- Zinc Ionophore Pyrithione Mimics CD28 Costimulatory Signal in CD3 Activated T Cells.International journal of molecular sciences · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Review
- Regulatory Role of Zinc in Immune Cell Signaling.Molecules and cells · 2021Review
- Zap70 Regulates TCR-Mediated Zip6 Activation at the Immunological Synapse.Frontiers in immunology · 2021Article
- Zinc as a Gatekeeper of Immune Function.Nutrients · 2017Review
- Metallothionein regulates intracellular zinc signaling during CD4(+) T cell activation.BMC immunology · 2016Article
- Article
- Age-Associated Failure To Adjust Type I IFN Receptor Signaling Thresholds after T Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Understanding immunosenescence to improve responses to vaccines.Nature immunology · 2013Review
- Immunosenescence, aging, and systemic lupus erythematous.Autoimmune diseases · 2013Review
- Signaling pathways in aged T cells - a reflection of T cell differentiation, cell senescence and host environment.Seminars in immunology · 2012Review
- Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity.Nature medicine · 2012Article
- Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Regulation of T cell receptor signaling by activation-induced zinc influx.The Journal of experimental medicine · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The ability to mount adaptive immune responses to vaccinations and viral infections declines with increasing age. To identify mechanisms leading to immunosenescence, primary CD4 T cell responses were examined in 60- to 75-year-old individuals lacking overt functional defects. Transcriptome analysis indicated a selective defect in zinc homeostasis. CD4 T cell activation was associated with zinc influx via the zinc transporter Zip6, leading to increased free cytoplasmic zinc and activation of negative feedback loops, including the induction of zinc-binding metallothioneins. In young adults, activation-induced cytoplasmic zinc concentrations declined after 2 days to below prestimulation levels. In contrast, activated naïve CD4 T cells from older individuals failed to downregulate cytoplasmic zinc, resulting in excessive induction of metallothioneins. Activation-induced metallothioneins regulated the redox state in activated T cells and accounted for an increased proliferation of old CD4 T cells, suggesting that regulation of T cell zinc homeostasis functions as a compensatory mechanism to preserve the replicative potential of naïve CD4 T cells with age.
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Registered trials
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