ArticleThe Journal of experimental medicine2004
Age-related CD8 T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed.
- The ageing immune system and its battle with viruses.The Journal of general virology · 2026Review
- Cellular hallmarks and aging clock of the human lung parenchyma.Nature communications · 2026Article
- Mitochondrial Transcription Factor A Deficiency in T Cells Leads to Activation of the Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase/Stimulator of Interferon Genes Pathway and Production of Autoantibodies in Mice.Journal of immunology research · 2026Article
- GNLY+CD8+ T cells bridge premature aging and persistent inflammation in people living with HIV.Emerging microbes & infections · 2025Article
- Single-cell sequencing on PBMCs from patients with HA and HB with inhibitors reveals different immune responses to FVIII and FIX.Blood advances · 2025Article
- Paracrine FGF21 dynamically modulates mTOR signaling to regulate thymus function across the lifespan.Nature aging · 2025Article
- A fundamental relationship between TCR diversity, repertoire size and systemic clonal expansion: insights from 30,000 TCRFrontiers in immunology · 2025Article
- Article
- Sequential Early-Life Infections Alter Peripheral Blood Transcriptomics in Aging Female Mice but Not the Response to De Novo Infection with Influenza Virus or M. tuberculosis.ImmunoHorizons · 2023Article
- Accessory cells precondition naïve T cells and regulatory T cells for cytokine-mediated proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Immune Phenotypes and Target Antigens of Clonally Expanded Bone Marrow T Cells in Treatment-Naïve Multiple Myeloma.Cancer immunology research · 2022Article
- Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets.The Journal of clinical investigation · 2022Article
- Headache Worsening after COVID-19 Vaccination: An Online Questionnaire-Based Study on 841 Patients with Migraine.Journal of clinical medicine · 2021Article
- Review
- Distinct organization of adaptive immunity in the long-lived rodent Spalax galili.Nature aging · 2021Article
- The impact of immuno-aging on SARS-CoV-2 vaccine development.GeroScience · 2021Review
- Age-Related Dynamics of Lung-Resident Memory CD8Frontiers in immunology · 2021Review
- Impact of Patient Age on Clinical Efficacy and Toxicity of Checkpoint Inhibitor Therapy.Frontiers in immunology · 2021Review
- Functional recreation of age-related CD8 T cells in young mice identifies drivers of aging- and human-specific tissue pathology.Mechanisms of ageing and development · 2020Article
- T-cell clones of uncertain significance are highly prevalent and show close resemblance to T-cell large granular lymphocytic leukemia. Implications for laboratory diagnostics.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
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Abstract
Peripheral T cell diversity is virtually constant in the young, but is invariably reduced in aged mice and humans. CD8+ T cell clonal expansions (TCE) are the most drastic manifestation of, and possible contributors to, this reduced diversity. We show that the presence of TCE results in reduced CD8+, but not CD4+, T cell diversity, and in functional inability to mobilize parts of the CD8+ T cell repertoire affected by TCE. In the model of herpes simplex virus (HSV)-1 infection of B6 mice, >90% of the responding CD8+ T cells use Vbeta10 or Vbeta8 and are directed against a single glycoprotein B (gB498-505) epitope, gB-8p. We found that old animals bearing CD8+ TCE within Vbeta10 or Vbeta8 families failed to mount an effective immune response against HSV-1, as judged by reduced numbers of peptide-major histocompatibility complex tetramer+ CD8 T cells and an absence of antiviral lytic function. Furthermore, Vbeta8 TCE experimentally introduced into young mice resulted in lower resistance to viral challenge, whereas Vbeta5+ TCE induced in a similar fashion did not impact viral resistance. These results demonstrate that age-related TCE functionally impair the efficacy of antiviral CD8+ T cell immunity in an antigen-specific manner, strongly suggesting that TCE are not the mere manifestation of, but are also a contributing factor to, the immunodeficiency of senescence.
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