ArticleThe Journal of experimental medicine2013
CD4+ T helper cells use CD154-CD40 interactions to counteract T reg cell-mediated suppression of CD8+ T cell responses to influenza.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- TScience advances · 2025Article
- Type 2 conventional dendritic cell functional heterogeneity: ontogenically committed or environmentally plastic?Trends in immunology · 2025Review
- Persistent Antigen Harbored by Alveolar Macrophages Enhances the Maintenance of Lung-Resident Memory CD8Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- SATB1 ensures appropriate transcriptional programs within naïve CD8Immunology and cell biology · 2022Article
- Review
- Pathogenesis of Respiratory Viral and Fungal Coinfections.Clinical microbiology reviews · 2022Review
- Regulation of Host Immune Responses against Influenza A Virus Infection by Mitogen-Activated Protein Kinases (MAPKs).Microorganisms · 2020Review
- Immunogenicity of Protein Therapeutics: A Lymph Node Perspective.Frontiers in immunology · 2020Review
- CD4Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Kinetics and Phenotype of the CD4 T Cell Response to Influenza Virus Infections.Frontiers in immunology · 2019Article
- The opposing roles of CD4Immunology · 2018Review
- Type 1 Conventional CD103Frontiers in immunology · 2018Article
- Role of CD4 T cell helper subsets in immune response and deviation of CD8 T cells in mice.European journal of immunology · 2017Article
- CD40-signalling abrogates induction of RORγtNature communications · 2017Article
- The multifaceted role of CD4(+) T cells in CD8(+) T cell memory.Nature reviews. Immunology · 2016Review
- New Insights into the Generation of CD4 Memory May Shape Future Vaccine Strategies for Influenza.Frontiers in immunology · 2016Review
- NADPH Oxidase 1 Is Associated with Altered Host Survival and T Cell Phenotypes after Influenza A Virus Infection in Mice.PloS one · 2016Article
- Genome-wide identification of allele-specific expression in response to Streptococcus suis 2 infection in two differentially susceptible pig breeds.Journal of applied genetics · 2015Article
- CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection.Immunity · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
CD4(+) T cells promote CD8(+) T cell priming by licensing dendritic cells (DCs) via CD40-CD154 interactions. However, the initial requirement for CD40 signaling may be replaced by the direct activation of DCs by pathogen-derived signals. Nevertheless, CD40-CD154 interactions are often required for optimal CD8(+) T cell responses to pathogens for unknown reasons. Here we show that CD40 signaling is required to prevent the premature contraction of the influenza-specific CD8(+) T cell response. CD40 is required on DCs but not on B cells or T cells, whereas CD154 is required on CD4(+) T cells but not CD8(+) T cells, NKT cells, or DCs. Paradoxically, even though CD154-expressing CD4(+) T cells are required for robust CD8(+) T cell responses, primary CD8(+) T cell responses are apparently normal in the absence of CD4(+) T cells. We resolved this paradox by showing that the interaction of CD40-bearing DCs with CD154-expressing CD4(+) T cells precludes regulatory T cell (T reg cell)-mediated suppression and prevents premature contraction of the influenza-specific CD8(+) T cell response. Thus, CD4(+) T helper cells are not required for robust CD8(+) T cell responses to influenza when T reg cells are absent.
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Identifiers
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.