ArticlePloS one2008
CTLA-4 activation of phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 47 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
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
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- Dual Checkpoint Aptamer Immunotherapy: Unveiling Tailored Cancer Treatment Targeting CTLA-4 and NKG2A.Cancers · 2024Article
- Targets of Immune Escape Mechanisms in Cancer: Basis for Development and Evolution of Cancer Immune Checkpoint Inhibitors.Biology · 2023Review
- Current understanding of CTLA-4: from mechanism to autoimmune diseases.Frontiers in immunology · 2023Review
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- Tafazzin deficiency in mouse mesenchymal stem cells promote reprogramming of activated B lymphocytes toward immunosuppressive phenotypes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
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- Landscape of alterations in the checkpoint system in myelodysplastic syndrome and implications for prognosis.PloS one · 2022Article
- Monoclonal Antibodies to CTLA-4 with Focus on Ipilimumab.Experientia supplementum (2012) · 2022Article
- Improving CAR T-Cell Persistence.International journal of molecular sciences · 2021Review
- Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8Cell death & disease · 2021Article
- How the Discovery of the CD4/CD8-p56Frontiers in cell and developmental biology · 2021Review
- Continuous Modeling of T CD4 Lymphocyte Activation and Function.Frontiers in immunology · 2021Article
- The Role of GSK-3 in Cancer Immunotherapy: GSK-3 Inhibitors as a New Frontier in Cancer Treatment.Cells · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
The balance of T-cell proliferation, anergy and apoptosis is central to immune function. In this regard, co-receptor CTLA-4 is needed for the induction of anergy and tolerance. One central question concerns the mechanism by which CTLA-4 can induce T-cell non-responsiveness without a concurrent induction of antigen induced cell death (AICD). In this study, we show that CTLA-4 activation of the phosphatidylinositol 3-kinase (PI 3-K) and protein kinase B (PKB/AKT) sustains T-cell anergy without cell death. CTLA-4 ligation induced PI 3K activation as evidenced by the phosphorylation of PKB/AKT that in turn inactivated GSK-3. The level of activation was similar to that observed with CD28. CTLA-4 induced PI 3K and AKT activation also led to phosphorylation of the pro-apoptotic factor BAD as well as the up-regulation of BcL-XL. In keeping with this, CD3/CTLA-4 co-ligation prevented apoptosis under the same conditions where T-cell non-responsiveness was induced. This effect was PI 3K and PKB/AKT dependent since inhibition of these enzymes under conditions of anti-CD3/CTLA-4 co-ligation resulted in cell death. Our findings therefore define a mechanism by which CTLA-4 can induce anergy (and possibly peripheral tolerance) by preventing the induction of cell death.
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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.