ArticleThe Journal of clinical investigation2004
Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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The trial behind it
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Who cites it
73 citing papers in PubMed, 147 citations in OpenAlex.
- The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.JCI insight · 2024Article
- Mucosal Addressin Cell Adhesion Molecule-1 Mediates T Cell Migration into Pancreas-Draining Lymph Nodes for Initiation of the Autoimmune Response in Type 1 Diabetes.International journal of molecular sciences · 2024Article
- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
- Activation pathways that drive CD4Immunological reviews · 2022Review
- Generation of hypoimmunogenic human pluripotent stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Ontology-based validation and identification of regulatory phenotypes.Bioinformatics (Oxford, England) · 2018Article
- CD28 blockade controls T cell activation to prevent graft-versus-host disease in primates.The Journal of clinical investigation · 2018Article
- Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.Cell stem cell · 2018Review
- Requirement for CD40/CD40L Interactions for Development of Autoimmunity Differs Depending on Specific Checkpoint and Costimulatory Pathways.ImmunoHorizons · 2018Article
- Circadian clock cryptochrome proteins regulate autoimmunity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction.Journal of medicinal chemistry · 2017Article
- Intracellular B Lymphocyte Signalling and the Regulation of Humoral Immunity and Autoimmunity.Clinical reviews in allergy & immunology · 2017Review
- Advances in targeting co-inhibitory and co-stimulatory pathways in transplantation settings: the Yin to the Yang of cancer immunotherapy.Immunological reviews · 2017Review
- The Future of Immunotherapy: A 20-Year Perspective.Frontiers in immunology · 2017Article
- PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells.PloS one · 2017Article
- Targeting innate immunity to downmodulate adaptive immunity and reverse type 1 diabetes.ImmunoTargets and therapy · 2017Review
- Singular role for T-BET+CXCR3+ regulatory T cells in protection from autoimmune diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Co-stimulatory and Co-inhibitory Pathways in Autoimmunity.Immunity · 2016Review
- Regulatory T and B lymphocytes in a spontaneous autoimmune polyneuropathy.Clinical and experimental immunology · 2016Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse results from a breakdown in tolerance to pancreatic islet antigens. CD28-B7 and CD40 ligand-CD40 (CD40L-CD40) costimulatory pathways affect the development of disease and are promising therapeutic targets. Indeed, it was shown previously that diabetes fails to develop in NOD-B7-2-/- and NOD-CD40L-/- mice. In this study, we examined the relative role of these 2 costimulatory pathways in the balance of autoimmunity versus regulation in NOD mice. We demonstrate that initiation but not effector function of autoreactive T cells was defective in NOD-B7-2-/- mice. Moreover, the residual proliferation of the autoreactive cells was effectively controlled by CD28-dependent CD4+CD25+ regulatory T cells (Treg's), as depletion of Treg's partially restored proliferation of autoreactive T cells and resulted in diabetes in an adoptive-transfer model. Similarly, disruption of the CD28-B7 pathway and subsequent Treg deletion restored autoimmunity in NOD-CD40L-/- mice. These results demonstrate that development of diabetes is dependent on a balance of pathogenic and regulatory T cells that is controlled by costimulatory signals. Thus, elimination of Treg's results in diabetes even in the absence of costimulation, which suggests a need for alternative strategies for immunotherapeutic approaches.
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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.