ArticlePLoS pathogens2014
Out-of-sequence signal 3 as a mechanism for virus-induced immune suppression of CD8 T cell responses.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.The Journal of allergy and clinical immunology · 2020Trial
- 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
- The mRNA-LNP vaccines - the good, the bad and the ugly?Frontiers in immunology · 2024Review
- Once upon a prime: DCs shape cancer immunity.Trends in cancer · 2023Review
- STAT3 Role in T-Cell Memory Formation.International journal of molecular sciences · 2022Review
- Implications of a 'Third Signal' in NK Cells.Cells · 2021Review
- Characterizing the Dysfunctional NK Cell: Assessing the Clinical Relevance of Exhaustion, Anergy, and Senescence.Frontiers in cellular and infection microbiology · 2020Review
- MAIT Cells Display a Specific Response to Type 1 IFN Underlying the Adjuvant Effect of TLR7/8 Ligands.Frontiers in immunology · 2020Article
- Costimulation Induces CD4 T Cell Antitumor Immunity via an Innate-like Mechanism.Cell reports · 2019Article
- Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies.Immunity · 2018Review
- Immunoregulatory pathways following strong inflammatory processes markedly impair CD4+ T cell responses.Human vaccines & immunotherapeutics · 2016Review
- Type I IFN Signaling Is Dispensable during Secondary Viral Infection.PLoS pathogens · 2016Article
- Article
- Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner.Journal of virology · 2016Article
- Disease-promoting effects of type I interferons in viral, bacterial, and coinfections.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2015Review
- Regulation of antiviral T cell responses by type I interferons.Nature reviews. Immunology · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Virus infections are known to induce a transient state of immune suppression often associated with an inhibition of T cell proliferation in response to mitogen or cognate-antigen stimulation. Recently, virus-induced immune suppression has been linked to responses to type 1 interferon (IFN), a signal 3 cytokine that normally can augment the proliferation and differentiation of T cells exposed to antigen (signal 1) and co-stimulation (signal 2). However, pre-exposure of CD8 T cells to IFN-inducers such as viruses or poly(I∶C) prior to antigen signaling is inhibitory, indicating that the timing of IFN exposure is of essence. We show here that CD8 T cells pretreated with poly(I∶C) down-regulated the IFN receptor, up-regulated suppressor of cytokine signaling 1 (SOCS1), and were refractory to IFNβ-induced signal transducers and activators of transcription (STAT) phosphorylation. When exposed to a viral infection, these CD8 T cells behaved more like 2-signal than 3-signal T cells, showing defects in short lived effector cell differentiation, reduced effector function, delayed cell division, and reduced levels of survival proteins. This suggests that IFN-pretreated CD8 T cells are unable to receive the positive effects that type 1 IFN provides as a signal 3 cytokine when delivered later in the signaling process. This desensitization mechanism may partially explain why vaccines function poorly in virus-infected individuals.
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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.