ArticleGene therapy2015
β-Cell-targeted blockage of PD1 and CTLA4 pathways prevents development of autoimmune diabetes and acute allogeneic islets rejection.
Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Successful treatment of nivolumab and ipilimumab triggered type 1 diabetes by using sodium-glucose transporter 2 inhibitor: a case report and systematic review.Frontiers in public health · 2023Pooled it
- Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles.Cell reports. Medicine · 2026Article
- Cell Therapy for Type 1 Diabetes Mellitus: a Review of Clinical Trials.Bulletin of experimental biology and medicine · 2025Review
- Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease.Cold Spring Harbor perspectives in medicine · 2025Review
- Cell Therapies and Gene Therapy for Diabetes: Current Progress.Current diabetes reviews · 2025Review
- AAV-mediated co-expression of an immunogenic transgene plus PD-L1 enables sustained expression through immunological evasion.Scientific reports · 2024Article
- Article
- Research progress of autoimmune diseases based on induced pluripotent stem cells.Frontiers in immunology · 2024Review
- Review
- Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor-induced diabetes.JCI insight · 2022Article
- Manufacturing clinical-grade human induced pluripotent stem cell-derived beta cells for diabetes treatment.Cell proliferation · 2022Review
- Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression.Science advances · 2022Article
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- Pancreatic β-Cell Development and Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- Leverage biomaterials to modulate immunity for type 1 diabetes.Frontiers in immunology · 2022Review
- Restoring normal islet mass and function in type 1 diabetes through regenerative medicine and tissue engineering.The lancet. Diabetes & endocrinology · 2021Review
- Local Immunomodulatory Strategies to Prevent Allo-Rejection in Transplantation of Insulin-Producing Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- New Aspects of Diabetes Research and Therapeutic Development.Pharmacological reviews · 2021Review
- Review
- The Role of Programmed Death-1 in Type 1 Diabetes.Current diabetes reports · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Protection of β cells from autoimmune destruction potentially cures type 1 diabetes mellitus (T1D). During antigen presentation, interactions between cytotoxic T-lymphocyte antigen-4 (CTLA4) and B7 molecules, or programmed death 1 (PD1) and its ligand PDL1, negatively regulate immune responses in a non-redundant manner. Here we employed β-cell-targeted adeno-associated virus serotype 8 (AAV8)-based vectors to overexpress an artificial PDL1-CTLA4Ig polyprotein or interleukin 10 (IL10). β-Cell-targeted expression of PDL1-CTLA4Ig or IL10 preserved β-cell mass and protected NOD mice from T1D development. When NOD mice were treated with vectors at early onset of hyperglycemia, PDL1-CTLA4Ig or IL10 alone failed to normalize the early onset of hyperglycemia. When drug-induced diabetic mice received major histocompatibility complex (MHC)-matched allo-islets, with or without pretreatment of the PDL1-CTLA4Ig-expressing vector, PDL1-CTLA4Ig-expressing islets were protected from rejection for at least 120 days. Similarly, transplantation of PDL1-CTLA4Ig-expressing MHC-matched islets into mice with established T1D resulted in protection of allo-islets from acute rejection, although islet grafts were eventually rejected. Thus the present study demonstrates the potent immuno-suppressive effects of β-cell-targeted PDL1-CTLA4Ig overexpression against T1D development and allo-islet rejection. The gene-based simultaneous inhibition of PD1 and CTLA4 pathways provides a unique strategy for immunosuppression-free tissue/organ transplantation, especially in the setting of no established autoimmunity.
Indexed as
Identifiers
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.