ArticleAging cell2015
Low-affinity TCR engagement drives IL-2-dependent post-thymic maintenance of naive CD4+ T cells in aged humans.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Aging-associated SATB1 deficiency remodels 3D genome architecture and transcriptional programs in naive CD4Science advances · 2026Article
- Impaired humoral and T helper cell responses to toxic shock syndrome toxin-1 (TSST-1) in granulomatosis with polyangiitis.Rheumatology (Oxford, England) · 2025Article
- Diverging effects of tumor necrosis factor inhibitors and conventional synthetic disease-modifying antirheumatic drugs on immunosenescence and inflammageing in rheumatoid arthritis: a cross-sectional analysis.Immunity & ageing : I & A · 2025Article
- Naïve T-cell decline is a significant contributor to expression changes in ageing blood.Frontiers in aging · 2024Article
- Age-associated remodeling of T cell immunity and metabolism.Cell metabolism · 2023Review
- T cell aging and Alzheimer's disease.Frontiers in immunology · 2023Review
- Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica.Frontiers in immunology · 2022Article
- Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica.Frontiers in medicine · 2022Review
- Mechanisms underlying T cell ageing.Nature reviews. Immunology · 2019Review
- Decreased Expression of Negative Immune Checkpoint VISTA by CD4+ T Cells Facilitates T Helper 1, T Helper 17, and T Follicular Helper Lineage Differentiation in GCA.Frontiers in immunology · 2019Article
- The full spectrum of human naive T cells.Nature reviews. Immunology · 2018Review
- Sepsis-Induced T Cell Immunoparalysis: The Ins and Outs of Impaired T Cell Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Parameters of the Immune System and Vitamin D Levels in Old Individuals.Frontiers in immunology · 2018Article
- Impact of Aging on the Frequency, Phenotype, and Function of CD161-Expressing T Cells.Frontiers in immunology · 2018Article
- Involvement of MicroRNAs in the Aging-Related Decline of CD28 Expression by Human T Cells.Frontiers in immunology · 2018Article
- Neonatal and adult recent thymic emigrants produce IL-8 and express complement receptors CR1 and CR2.JCI insight · 2017Article
- An Explorative Biomarker Study for Vaccine Responsiveness after a Primary Meningococcal Vaccination in Middle-Aged Adults.Frontiers in immunology · 2017Article
- Changes in peripheral immune cell numbers and functions in octogenarian walkers - an acute exercise study.Immunity & ageing : I & A · 2017Article
- Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females.Scientific reports · 2016Article
- Neonatal thymectomy reveals differentiation and plasticity within human naive T cells.The Journal of clinical investigation · 2016Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insight into the maintenance of naive T cells is essential to understand defective immune responses in the context of aging and other immune compromised states. In humans, naive CD4+ T cells, in contrast to CD8+ T cells, are remarkably well retained with aging. Here, we show that low-affinity TCR engagement is the main driving force behind the emergence and accumulation of naive-like CD4+ T cells with enhanced sensitivity to IL-2 in aged humans. In vitro, we show that these CD45RA(+) CD25(dim) CD4(+) T cells can develop from conventional naive CD25(-) CD4+ T cells upon CD3 cross-linking alone, in the absence of costimulation, rather than via stimulation by the homeostatic cytokines IL-2, IL-7, or IL-15. In vivo, TCR engagement likely occurs in secondary lymphoid organs as these cells were detected in lymph nodes and spleen where they showed signs of recent activation. CD45RA(+) CD25(dim) CD4+ T cells expressed a broad TCRVβ repertoire and could readily differentiate into functional T helper cells. Strikingly, no expansion of CD45RA(+) CD25(dim) CD8+ T cells was detected with aging, thereby implying that maintenance of naive CD4+ T cells is uniquely regulated. Our data provide novel insight into the homeostasis of naive T cells and may guide the development of therapies to preserve or restore immunity in the elderly.
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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.