ArticlePloS one2015
Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 30 citations in OpenAlex.
- Distinct peripheral blood molecular signature emerges with successful tacrolimus withdrawal in kidney transplant recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Trial
- Sequential immunotherapy: towards cures for autoimmunity.Nature reviews. Drug discovery · 2024Review
- PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies.Cancer immunology, immunotherapy : CII · 2023Review
- Belatacept inhibit human B cell germinal center development in immunodeficient mice.Scientific reports · 2023Article
- CTLA4-Ig treatment induces M1-M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients.Arthritis research & therapy · 2021Article
- CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus.International journal of molecular sciences · 2021Article
- Reversible suppression of T cell function in the bone marrow microenvironment of acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- AP-1 activity induced by co-stimulation is required for chromatin opening during T cell activation.The Journal of experimental medicine · 2020Article
- Co-stimulatory and co-inhibitory pathways in cancer immunotherapy.Advances in cancer research · 2019Review
- Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis-Insights From Other Diseases.Frontiers in immunology · 2019Review
- Skin xenotransplantation: Historical review and clinical potential.Burns : journal of the International Society for Burn Injuries · 2018Review
- Refractory T-Cell Anergy and Rapidly Fatal Progressive Multifocal Leukoencephalopathy After Prolonged CTLA4 Therapy.Open forum infectious diseases · 2017Article
- The soluble cytoplasmic tail of CD45 (ct-CD45) in human plasma contributes to keep T cells in a quiescent state.European journal of immunology · 2017Article
- CD28 Costimulation: From Mechanism to Therapy.Immunity · 2016Review
- BioWardrobe: an integrated platform for analysis of epigenomics and transcriptomics data.Genome biology · 2015Article
- Tolerogenic Dendritic Cells on Transplantation: Immunotherapy Based on Second Signal Blockage.Journal of immunology research · 2015Review
- In vitro and in vivo immune assessments of genetically-engineered pig skin grafts in New World (squirrel) monkeys.XenotransplantationArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation, yet murine studies suggested that CTLA4-Ig could be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study the effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-κB and AP-1 transcription factors followed by a profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of the TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig-induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor.
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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.