ArticleJCI insight2017
High pathogen burden in childhood promotes the development of unconventional innate-like CD8+ T cells.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Immunological effects of nivolumab immunotherapy in patients with oral cavity squamous cell carcinoma.BMC cancer · 2020Trial
- Elucidating Immune Cell Mediated Causal Pathways Linking Blood Metabolites to Major Depressive Disorder: A Mediation Mendelian Randomization Analysis.Brain and behavior · 2026Article
- Infection vs. Reinfection: The Immunomodulation of Erythropoiesis.International journal of molecular sciences · 2024Article
- Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies.Life science alliance · 2023Article
- Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response.PLoS neglected tropical diseases · 2022Article
- An expanded population of CD8Frontiers in cell and developmental biology · 2022Article
- Multifunctional, TNF-α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8Frontiers in immunology · 2021Article
- Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage.PLoS pathogens · 2020Article
- Distinct PLZFJournal of immunology (Baltimore, Md. : 1950) · 2019Article
- Repeated clinical malaria episodes are associated with modification of the immune system in children.BMC medicine · 2019Article
- Reduced Expression of Immune Mediators by T-Cell Subpopulations of Combat-Exposed Veterans With Post-Traumatic Stress Disorder.Frontiers in psychiatry · 2019Article
- Chronic HIV-1 Infection Alters the Cellular Distribution of FcγRIIIa and the Functional Consequence of the FcγRIIIa-F158V Variant.Frontiers in immunology · 2019Article
- Cytotoxic CD8Nature medicine · 2018Article
- Interaction among smoking status, single nucleotide polymorphisms and markers of systemic inflammation in healthy individuals.Immunology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Cellular and humoral constituents of the immune system differ significantly between children and adults, yet very little is known about the impact of early-life pathogen exposure on this immunologic transition. We examined CD4+ and CD8+ T cell subsets defined by CCR7 and CD45RA expression in two longitudinal pediatric cohorts experiencing divergent levels of pathogen burden. Using multiparameter flow cytometry, along with serological, cytokine, and transcriptomic data, we show that cumulative pathogen burden promotes the development of atypical CD8dim T cells with an innate-like profile (Granzyme Bhi, IFNγlow, TNFαlow, PLFZhi, ID2hi, IKZF2hi) in contrast to age-matched children residing in a low pathogen-exposure area who display a more conventional CD8bright profile (IFNγ+, TNFα+, CCL4+). Furthermore, these unconventional T cells had stunted proliferation, distinct transcriptional programs, and impaired T cell receptor signaling and were enriched in hallmark TNFα, NF-κB, and IL-6 gene signaling pathways, reminiscent of NK cells and type-1 innate lymphoid cells. Our findings suggest that these unconventional CD8dim T cells arise in a very particular immunological context and may provide a deeper understanding of the heterogeneity in human immune responses.
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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.