ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Human neonatal naive CD4+ T cells have enhanced activation-dependent signaling regulated by the microRNA miR-181a.
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 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- From animal models to NAMs: a paradigm shift in developmental immunotoxicity testing.Archives of toxicology · 2026Review
- Development of systemic and mucosal immune responses against gut microbiota in early life and implications for the onset of allergies.Frontiers in allergy · 2024Review
- Larval T Cells Are Functionally Distinct from Adult T Cells in Xenopus laevis.ImmunoHorizons · 2023Article
- Epigenetic regulation of pediatric and neonatal immune responses.Pediatric research · 2022Review
- Hallmarks of the aging T-cell system.The FEBS journal · 2021Review
- miR-181a-regulated pathways in T-cell differentiation and aging.Immunity & ageing : I & A · 2021Review
- Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders.Frontiers in immunology · 2021Review
- A Genetic Model Reveals Biological Features of Neonatal CD4 Helper Cells Undergone Homeostasis in Mice.Frontiers in cell and developmental biology · 2021Article
- The early life education of the immune system: Moms, microbes and (missed) opportunities.Gut microbes · 2020Review
- Higher Frequency and Increased Expression of Molecules Associated with Suppression on T Regulatory Cells from Newborn Compared with Adult Nonhuman Primates.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Challenges for the Newborn Immune Response to Respiratory Virus Infection and Vaccination.Vaccines · 2020Review
- MicroRNA miR-181-A Rheostat for TCR Signaling in Thymic Selection and Peripheral T-Cell Function.International journal of molecular sciences · 2020Review
- Neonatal T Cells: A Reinterpretation.Annual review of immunology · 2020Review
- Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health.Frontiers in immunology · 2020Review
- Challenges for the Newborn Following Influenza Virus Infection and Prospects for an Effective Vaccine.Frontiers in immunology · 2020Review
- Dysregulated Mucosal Immunity and Associated Pathogeneses in Preterm Neonates.Frontiers in immunology · 2020Review
- IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis.Journal of Cancer · 2020Article
- Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Contribution of ROS and metabolic status to neonatal and adult CD8+ T cell activation.PloS one · 2019Article
- Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Compared with older children and adults, human neonates have reduced and delayed CD4(+) T cell immunity to certain pathogens, but the mechanisms for these developmental differences in immune function remain poorly understood. We investigated the hypothesis that impaired human neonatal CD4(+) T cell immunity was due to reduced signaling by naive CD4(+) T cells following engagement of the αβ-TCR/CD3 complex and CD28. Surprisingly, calcium flux following engagement of CD3 was significantly higher in neonatal naive CD4(+) T cells from umbilical cord blood (CB) compared with naive CD4(+) T cells from adult peripheral blood. Enhanced calcium flux was also observed in adult CD4(+) recent thymic emigrants. Neonatal naive CD4(+) T cells also had higher activation-induced Erk phosphorylation. The microRNA miR-181a, which enhances activation-induced calcium flux in murine thymocytes, was expressed at significantly higher levels in CB naive CD4(+) T cells compared with adult cells. Overexpression of miR-181a in adult naive CD4(+) T cells increased activation-induced calcium flux, implying that the increased miR-181a levels of CB naive CD4(+) T cells contributed to their enhanced signaling. In contrast, AP-1-dependent transcription, which is downstream of Erk and required for full T cell activation, was decreased in CB naive CD4(+) T cells compared with adult cells. Thus, CB naive CD4(+) T cells have enhanced activation-dependent calcium flux, indicative of the retention of a thymocyte-like phenotype. Enhanced calcium signaling and Erk phosphorylation are decoupled from downstream AP-1-dependent transcription, which is reduced and likely contributes to limitations of human fetal and neonatal CD4(+) T cell immunity.
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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.