ArticleImmunity2015
Out-of-Sequence Signal 3 Paralyzes Primary CD4(+) T-Cell-Dependent Immunity.
Article in Immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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
67 citing papers in PubMed, 105 citations in OpenAlex.
- OX40 Ligand/OX40 Axis as the Inflammatory Prequel in Atopic Dermatitis: A Narrative Review.Dermatology and therapy · 2026Review
- CD4Journal for immunotherapy of cancer · 2026Article
- Delayed type I interferon response and the subsequent out-of-sequence cytokine signal inhibit T cell induction in non-surviving Ebola virus-infected patients.Frontiers in immunology · 2026Article
- In vitro protocol demonstrating five functional steps of trained immunity in mice: Implications on biomarker discovery and translational research.Cell reports · 2025Article
- A vascular-associated fibroblastic cell controls pancreatic islet immunity.Cell reports · 2025Article
- Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases.Molecular therapy. Methods & clinical development · 2025Review
- Review
- Molecular insights into T cell development, activation and signal transduction (Review).Biomedical reports · 2025Review
- Multi-disciplinary approaches paving the way for clinically effective peptide vaccines for cancer.NPJ vaccines · 2025Review
- Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.Cell systems · 2025Article
- Immunotherapy in gastrointestinal cancers: current strategies and future directions - a literature review.Annals of medicine and surgery (2012) · 2025Review
- Effects of combined radiotherapy with immune checkpoint blockade on immunological memory in luminal-like subtype murine bladder cancer model.Cancer biology & therapy · 2024Article
- T Cell Resistance: On the Mechanisms of T Cell Non-activation.Immune network · 2024Review
- Engineering potent chimeric antigen receptor T cells by programming signaling during T-cell activation.Scientific reports · 2024Article
- Immunotherapy: The Fourth Domain in Oral Cancer Therapeutics.Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India · 2024Article
- Therapeutic induction of antigen-specific immune tolerance.Nature reviews. Immunology · 2024Review
- A comparison of clustering models for inference of T cell receptor antigen specificity.Immunoinformatics (Amsterdam, Netherlands) · 2024Article
- Design and Evaluation of Synthetic Delivery Formulations for Peptide-Based Cancer Vaccines.BME frontiers · 2024Article
- Posttranscriptional Events Orchestrate Immune Homeostasis of CD8Methods in molecular biology (Clifton, N.J.) · 2024Review
- Monocytes as an early risk factor for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.Frontiers in immunology · 2024Article
7 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
17 authors at 8 institutions in 2 countries.
Funding
Abstract
Primary T cell activation involves the integration of three distinct signals delivered in sequence: (1) antigen recognition, (2) costimulation, and (3) cytokine-mediated differentiation and expansion. Strong immunostimulatory events such as immunotherapy or infection induce profound cytokine release causing "bystander" T cell activation, thereby increasing the potential for autoreactivity and need for control. We show that during strong stimulation, a profound suppression of primary CD4(+) T-cell-mediated immune responses ensued and was observed across preclinical models and patients undergoing high-dose interleukin-2 (IL-2) therapy. This suppression targeted naive CD4(+) but not CD8(+) T cells and was mediated through transient suppressor of cytokine signaling-3 (SOCS3) inhibition of the STAT5b transcription factor signaling pathway. These events resulted in complete paralysis of primary CD4(+) T cell activation, affecting memory generation and induction of autoimmunity as well as impaired viral clearance. These data highlight the critical regulation of naive CD4(+) T cells during inflammatory conditions.
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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.