ArticleJournal of immunology (Baltimore, Md. : 1950)2013
IFN-α inhibits telomerase in human CD8⁺ T cells by both hTERT downregulation and induction of p38 MAPK signaling.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 59 citations in OpenAlex.
- Review
- Regulation of T Cell Senescence in Health and Diseases.Immune network · 2026Review
- Immunoregulatory mechanisms in the aging microenvironment: Targeting the senescence-associated secretory phenotype for cancer immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Expanded senescent CD8 T cells in IMID patients are associated with distinct inflammatory cytokines.Clinical and experimental immunology · 2025Article
- Immune cell senescence in autoimmunity: implications for disease pathogenesis and therapeutic targeting.Frontiers in immunology · 2025Review
- T-Cell Senescence in Human Metabolic Diseases.Diabetes & metabolism journal · 2024Review
- Investigating the role of senescence biomarkers in colorectal cancer heterogeneity by bulk and single-cell RNA sequencing.Scientific reports · 2024Article
- Human platelet lysate enhances in vivo activity of CAR-Vδ2 T cells by reducing cellular senescence and apoptosis.Cytotherapy · 2024Article
- Deciphering the impact of TERT/telomerase on immunosenescence and T cell revitalization.Frontiers in immunology · 2024Review
- Human virome profiling identified CMV as the major viral driver of a high accumulation of senescent CD8Science advances · 2023Article
- Chronic inflammation and the hallmarks of aging.Molecular metabolism · 2023Review
- The central role of DNA damage in immunosenescence.Frontiers in aging · 2023Review
- Senescent CD4International journal of molecular sciences · 2022Review
- Knowns and Unknowns about CAR-T Cell Dysfunction.Cancers · 2022Review
- Premature Senescence of T-cells Favors Bone Loss During Osteolytic Diseases. A New Concern in the Osteoimmunology Arena.Aging and disease · 2021Article
- Review
- Aging-associated immune system changes in multiple myeloma: The dark side of the moon.Cancer treatment and research communications · 2021Review
- hTERT Transduction Extends the Lifespan of Primary Pediatric Low-Grade Glioma Cells While Preserving the Biological Response to NGF.Pathology oncology research : POR · 2021Article
- Induction of T Cell Senescence by Cytokine Induced Bystander Activation.Frontiers in aging · 2021Review
- Senescence in the Development and Response to Cancer with Immunotherapy: A Double-Edged Sword.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 4 countries.
Funding
Abstract
The cytokine IFN-α is secreted during viral infections and has been shown to inhibit telomerase activity and accelerate T cell differentiation in vivo. However, the mechanism for this inhibition is not clear. In this study, we show that IFN-α inhibits both the transcription and translation of human telomerase reverse transcriptase (hTERT), the catalytic component of telomerase, in activated CD8(+) T cells. This was associated with increased activity of the repressor of hTERT transcription E2 transcription factor and decreased activation of NF-κB that promotes hTERT transcription. However IFN-α did not affect the translocation of hTERT from the cytoplasm to the nucleus. IFN-α also inhibits AKT kinase activation but increases p38 MAPK activity, and both of these events have been shown previously to inhibit telomerase activity. Addition of BIRB796, an inhibitor of p38 activity, to IFN-α-treated cells reversed, in part, the inhibition of telomerase by this cytokine. Therefore, IFN-α can inhibit the enzyme telomerase in CD8(+) T cells by transcriptional and posttranslational mechanisms. Furthermore, the addition of IFN-α to CD8(+)CD27(+)CD28(+) T cells accelerates the loss of both these costimulatory molecules. This suggests that persistent viral infections may contribute to the accumulation of highly differentiated/senescent CD8(+)CD27(-)CD28(-) T cells during aging by promoting IFN-α secretion during repeated episodes of viral reactivation.
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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.