ArticlePloS one2009
Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 80 citations in OpenAlex.
- Dynamics of a cytokine storm.PloS one · 2012Trial
- Regulatory T cells as a potential treatment for autoimmune inflammatory rheumatic and musculoskeletal diseases.Clinical rheumatology · 2026Review
- Dimethyl Sulfoxide Modulates T Cell-Mediated Immunity to Attenuate Influenza A Virus Infection.Journal of inflammation research · 2026Article
- Cord blood-derived iNK T cells as a platform for allogeneic CAR T cell therapy.Frontiers in immunology · 2025Article
- Review
- Platelet Dysregulation in the Pathobiology of COVID-19.Hamostaseologie · 2022Review
- Modulating cholesterol-rich lipid rafts to disrupt influenza A virus infection.Frontiers in immunology · 2022Review
- Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19.Frontiers in immunology · 2022Article
- The 'cytokine storm': molecular mechanisms and therapeutic prospects.Trends in immunology · 2021Review
- Review
- Tobacco, but Not Nicotine and Flavor-Less Electronic Cigarettes, Induces ACE2 and Immune Dysregulation.International journal of molecular sciences · 2020Article
- Treatment of mice with a ligand binding blocking anti-CD28 monoclonal antibody improves healing after myocardial infarction.PloS one · 2020Article
- The promise of CD4Haematologica · 2019Review
- What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.Cold Spring Harbor perspectives in biology · 2018Review
- Proliferation of endogenous regulatory T cells improve the pathophysiology associated with placental ischaemia of pregnancy.American journal of reproductive immunology (New York, N.Y. : 1989) · 2017Article
- Regulatory T cells ameliorate intracerebral hemorrhage-induced inflammatory injury by modulating microglia/macrophage polarization through the IL-10/GSK3β/PTEN axis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Friend or foe: the dichotomous impact of T cells on neuro-de/re-generation during aging.Oncotarget · 2017Review
- Self-Recognition Sensitizes Mouse and Human Regulatory T Cells to Low-Dose CD28 Superagonist Stimulation.Frontiers in immunology · 2017Article
- Editorial: The Molecular Mechanisms of Cyclic AMP in Regulation of Immunity and Tolerance.Frontiers in immunology · 2017Article
- CD28 superagonist-mediated boost of regulatory T cells increases thrombo-inflammation and ischemic neurodegeneration during the acute phase of experimental stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Superagonistic CD28-specific monoclonal antibodies (CD28SA) are highly effective activators of regulatory T-cells (Treg cells) in rats, but a first-in-man trial of the human CD28SA TGN1412 resulted in an unexpected cytokine release syndrome. Using a novel mouse anti-mouse CD28SA, we re-investigate the relationship between Treg activation and systemic cytokine release. Treg activation by CD28SA was highly efficient but depended on paracrine IL-2 from CD28SA-stimulated conventional T-cells. Systemic cytokine levels were innocuous, but depletion of Treg cells prior to CD28SA stimulation led to systemic release of proinflammatory cytokines, indicating that in rodents, Treg cells effectively suppress the inflammatory response. Since the human volunteers of the TGN1412 study were not protected by this mechanism, we also tested whether corticosteroid prophylaxis would be compatible with CD28SA induced Treg activation. We show that neither the expansion nor the functional activation of Treg cells is affected by high-dose dexamethasone sufficient to control systemic cytokine release. Our findings warn that preclinical testing of activating biologicals in rodents may miss cytokine release syndromes due to the rapid and efficacious response of the rodent Treg compartment, and suggest that polyclonal Treg activation is feasible in the presence of antiphlogistic corticosteroid prophylaxis.
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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.