ArticleThe Journal of clinical investigation2008
A CD28 superagonistic antibody elicits 2 functionally distinct waves of T cell activation in rats.
Article in The Journal of clinical investigation, 2008. 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 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
16 citing papers in PubMed, 46 citations in OpenAlex.
- Article
- CD28 Superagonist Shock and Blockage of Motogenic T Cell Cascade.Frontiers in immunology · 2021Review
- Immunopathogenesis and treatment of cytokine storm in COVID-19.Theranostics · 2021Review
- Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity.Journal of neuroinflammation · 2019Article
- Article
- Delivering safer immunotherapies for cancer.Advanced drug delivery reviews · 2017Review
- Article
- Human and mouse CD137 have predominantly different binding CRDs to their respective ligands.PloS one · 2014Article
- Granzyme B- and Fas ligand-mediated cytotoxic function induced by mitogenic CD28 stimulation of human memory CD4+ T cells.Journal of leukocyte biology · 2012Article
- Blood cytokines as biomarkers of in vivo toxicity in preclinical safety assessment: considerations for their use.Toxicological sciences : an official journal of the Society of Toxicology · 2010Review
- Inhibitor of NF-kappa B kinases alpha and beta are both essential for high mobility group box 1-mediated chemotaxis [corrected].Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- The safety and side effects of monoclonal antibodies.Nature reviews. Drug discovery · 2010Review
- Article
- Models of autoimmune demyelination in the central nervous system: on the way to translational medicine.Experimental & translational stroke medicine · 2009Article
- Rapid regulatory T-cell response prevents cytokine storm in CD28 superagonist treated mice.PloS one · 2009Article
- The calm after the cytokine storm: lessons from the TGN1412 trial.The Journal of clinical investigation · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Administration of the CD28 superagonistic antibody JJ316 is an efficient means to treat autoimmune diseases in rats, but the humanized antibody TGN1412 caused devastating side effects in healthy volunteers during a clinical trial. Here we show that JJ316 treatment of rats induced a dramatic redistribution of T lymphocytes from the periphery to the secondary lymphoid organs, resulting in severe T lymphopenia. Live imaging of secondary lymphoid organs revealed that JJ316 administration almost instantaneously (<2 minutes) arrested T cells in situ. This reduction in T cell motility was accompanied by profound cytoskeletal rearrangements and increased cell size. In addition, surface expression of lymphocyte function-associated antigen-1 was enhanced, endothelial differentiation sphingolipid G protein-coupled receptor 1 and L selectin levels were downregulated, and the cells lost their responsiveness to sphingosine 1-phosphate-directed migration. These proadhesive alterations were accompanied by signs of strong activation, including upregulation of CD25, CD69, CD134, and proinflammatory mediators. However, this did not lead to a cytokine storm similar to the clinical trial. While most of the early changes disappeared within 48 hours, we observed that CD4+CD25+FoxP3+ regulatory T cells experienced a second phase of activation, which resulted in massive cell enlargement, extensive polarization, and increased motility. These data suggest that CD28 superagonists elicit 2 qualitatively distinct waves of activation.
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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.