ArticleThe Journal of clinical investigation2006
Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.
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Who cites it
133 citing papers in PubMed, 1 synthesis or guideline pooled it, 285 citations in OpenAlex.
- Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group.Clinical and experimental immunology · 2010Guideline
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- 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
- Experimental Models to Study Diabetes Mellitus and Its Complications: Limitations and New Opportunities.International journal of molecular sciences · 2023Review
- Innovative Designs and Logistical Considerations for Expedited Clinical Development of Combination Disease-Modifying Treatments for Type 1 Diabetes.Diabetes care · 2022Review
- Reduction of Cell Surface T-Cell Receptor by Non-Mitogenic CD3 Antibody to Mitigate Murine Lupus.Frontiers in immunology · 2022Article
- Cytolytic CD4Frontiers in immunology · 2022Review
- Leverage biomaterials to modulate immunity for type 1 diabetes.Frontiers in immunology · 2022Review
- Preventing type 1 diabetes in late-stage pre-diabetic NOD mice with insulin: A central role for alum as adjuvant.Frontiers in endocrinology · 2022Article
- From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes.Frontiers in medicine · 2022Review
- Syntaxin 4 Enrichment in β-Cells Prevents Conversion to Autoimmune Diabetes in Non-Obese Diabetic (NOD) Mice.Diabetes · 2021Article
- Formation of pancreatic β-cells from precursor cells contributes to the reversal of established type 1 diabetes.Cellular immunology · 2021Article
- GABABiomedicines · 2021Article
- Antigen-Specific Regulatory T Cell Therapy in Autoimmune Diseases and Transplantation.Frontiers in immunology · 2021Review
- RecombinantJournal of diabetes research · 2021Article
- Dextran Sulfate Protects Pancreatic β-Cells, Reduces Autoimmunity, and Ameliorates Type 1 Diabetes.Diabetes · 2020Article
- Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention.Cell metabolism · 2020Article
- Chemokines as Drivers of the Autoimmune Destruction in Type 1 Diabetes: Opportunity for Therapeutic Intervention in Consideration of an Optimal Treatment Schedule.Frontiers in endocrinology · 2020Review
- Stimulator of interferon genes agonists attenuate type I diabetes progression in NOD mice.Immunology · 2019Article
- Homotaurine Treatment Enhances CD4ImmunoHorizons · 2019Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Safe induction of autoantigen-specific long-term tolerance is the "holy grail" for the treatment of autoimmune diseases. In animal models of type 1 diabetes, oral or i.n. immunization with islet antigens induces Tregs that are capable of bystander suppression. However, such interventions are only effective early in the prediabetic phase. Here, we demonstrate that a novel combination treatment with anti-CD3epsilon-specific antibody and i.n. proinsulin peptide can reverse recent-onset diabetes in 2 murine diabetes models with much higher efficacy than with monotherapy with anti-CD3 or antigen alone. In vivo, expansion of CD25(+)Foxp3(+) and insulin-specific Tregs producing IL-10, TGF-beta, and IL-4 was strongly enhanced. These cells could transfer dominant tolerance to immunocompetent recent-onset diabetic recipients and suppressed heterologous autoaggressive CD8 responses. Thus, combining a systemic immune modulator with antigen-specific Treg induction is more efficacious in reverting diabetes. Since Tregs act site-specifically, this strategy should also be expected to reduce the potential for systemic side effects.
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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.