ArticleScience translational medicine2011
Functional regulatory T cells produced by inhibiting cyclic nucleotide phosphodiesterase type 3 prevent allograft rejection.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 67 citations in OpenAlex.
- Pde1b controls cyclic nucleotide signaling in cDC1 and macrophages to regulate immune responses.EMBO reports · 2026Article
- A mini-review: phosphodiesterases in charge to balance intracellular cAMP during T-cell activation.Frontiers in immunology · 2024Review
- Linked sensitization by memory CD4+ T cells prevents costimulation blockade-induced transplantation tolerance.JCI insight · 2022Article
- Upregulation of Phosphodiesterase 2A Augments T Cell Activation by Changing cGMP/cAMP Cross-Talk.Frontiers in pharmacology · 2021Article
- Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions.International journal of molecular sciences · 2020Review
- Central Roles of OX40L-OX40 Interaction in the Induction and Progression of Human T Cell-Driven Acute Graft-versus-Host Disease.ImmunoHorizons · 2019Article
- Targeting Adenosine in Cancer Immunotherapy to Enhance T-Cell Function.Frontiers in immunology · 2019Review
- Engineering therapeutic T cells to suppress alloimmune responses using TCRs, CARs, or BARs.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Review
- A Rapamycin-Based GMP-Compatible Process for the Isolation and Expansion of Regulatory T Cells for Clinical Trials.Molecular therapy. Methods & clinical development · 2018Article
- A simplified cuff technique for abdominal aortic transplantation in mice.The Journal of surgical research · 2016Article
- Blocking MHC class II on human endothelium mitigates acute rejection.JCI insight · 2016Article
- Regulatory T-Cell-Mediated Suppression of Conventional T-Cells and Dendritic Cells by Different cAMP Intracellular Pathways.Frontiers in immunology · 2016Review
- Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases.Inflammatory bowel diseases · 2015Review
- Cell therapy to induce allograft tolerance: time to switch to plan B?Frontiers in immunology · 2015Review
- Transplantation tolerance.Pediatric nephrology (Berlin, Germany) · 2014Review
- Transplantation tolerance and its outcome during infections and inflammation.Immunological reviews · 2014Review
- Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study.Transplantation research · 2013Article
- Promoting transplantation tolerance; adoptive regulatory T cell therapy.Clinical and experimental immunology · 2013Review
- Adenosine and prostaglandin e2 production by human inducible regulatory T cells in health and disease.Frontiers in immunology · 2013Article
- Do Natural T Regulatory Cells become Activated to Antigen Specific T Regulatory Cells in Transplantation and in Autoimmunity?Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Regulatory T cells (T(regs)) manipulated ex vivo have potential as cellular therapeutics in autoimmunity and transplantation. Although it is possible to expand naturally occurring T(regs), an attractive alternative possibility, particularly suited to solid organ and bone marrow transplantation, is the stimulation of total T cell populations with defined allogeneic antigen-presenting cells (APCs) under conditions that lead to the generation or expansion of donor-reactive, adaptive T(regs). Here we demonstrate that stimulation of mouse CD4(+) T cells by immature allogeneic dendritic cells combined with pharmacological inhibition of phosphodiesterase 3 (PDE) resulted in a functional enrichment of Foxp3(+) T cells. Without further manipulation or selection, the resultant population delayed skin allograft rejection mediated by polyclonal CD4(+) effectors or donor-reactive CD8(+) T cell receptor transgenic T cells and inhibited both effector cell proliferation and T cell priming for interferon-γ production. Notably, PDE inhibition also enhanced the enrichment of human Foxp3(+) CD4(+) T cells driven by allogeneic APCs. These cells inhibited T cell proliferation in a standard in vitro mixed lymphocyte assay and, moreover, attenuated the development of vasculopathy mediated by autologous peripheral blood mononuclear cells in a functionally relevant humanized mouse transplant model. These data establish a method for the ex vivo generation of graft-reactive, functional mouse and human T(regs) that uses a clinically approved agent, making pharmacological PDE inhibition a potential strategy for T(reg)-based therapies.
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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.