ArticleProceedings of the National Academy of Sciences of the United States of America2015
Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
215 citing papers in PubMed, 1 synthesis or guideline pooled it, 309 citations in OpenAlex.
- Structural Basis for CD4+ T Cell Epitope Dominance in Arbo-Flavivirus Envelope Proteins: A Meta-Analysis.Viral immunology · 2017Pooled it
- Reference range of naïve T and T memory lymphocyte subsets in peripheral blood of healthy adult.Clinical and experimental immunology · 2022Trial
- Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis.The Journal of clinical investigation · 2020Trial
- Association of dengue virus-specific polyfunctional T-cell responses with clinical disease severity in acute dengue infection.Immunity, inflammation and disease · 2019Trial
- Bridging Efficacy of a Tetravalent Dengue Vaccine from Children/Adolescents to Adults in Highly Endemic Countries Based on Neutralizing Antibody Response.The American journal of tropical medicine and hygiene · 2019Trial
- Dengue vaccines: The role of a correlate of protection in evaluating vaccine safety and risk.Vaccine · 2026Article
- CD151 identifies a cytotoxic CD4 T cell population enriched in people with HIV that later develop cancer.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Cytotoxic CD4Parasite immunology · 2026Article
- Long-term antibody dynamics challenge the paradigm of lifelong homotypic immunity to dengue virus.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Heterologous vaccination with a next-generation vaccinia virus and Ad26 induces Ebola-specific immunity in macaques.NPJ vaccines · 2026Article
- Dynamic landscape of peripheral blood lymphocyte subsets in dengue patients: a multimodal single-cell and flow cytometry analysis.BMC infectious diseases · 2026Article
- Chemokine Receptor Profile of Circulating Leukocyte Subsets in Response to Acute High-Intensity Interval Training.Biomolecules · 2026Article
- Integrating multi-omic QTLs and predictive models reveals regulatory architectures at immune related GWAS loci in CD4+ T cells.medRxiv : the preprint server for health sciences · 2026Article
- A distinct subset of stem-cell memory is poised for the cytotoxicity program in CD4Science advances · 2026Article
- T Cell Responses During Dengue Infection.Current topics in microbiology and immunology · 2026Review
- Mapping immune responses to TAK-003 dengue vaccine: immunogenicity across the clinical development program.Frontiers in immunology · 2026Review
- Cytotoxic CD4+ T cells in cancer: an emerging target for next-generation anticancer immunotherapy?Journal for immunotherapy of cancer · 2025Review
- Dengue and severe dengue.Clinical microbiology reviews · 2025Review
- LANA-specific CD4Nature communications · 2025Article
- Review
155 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8(+) T-cell responses have been extensively studied, the breadth and specificity of CD4(+) T-cell responses remains to be defined. Here we define HLA-restricted CD4(+) T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4(+) T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1(+) Eomesodermin(+) perforin(+) granzyme B(+) CD45RA(+) CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4(+) T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.
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What OpenQuestion holds
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.