ArticleDiabetologia2010
Subcutaneous insulin B:9-23/IFA immunisation induces Tregs that control late-stage prediabetes in NOD mice through IL-10 and IFNgamma.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
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- 2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration.Inflammation and regeneration · 2022Article
- Editing T cell repertoire by thymic epithelial cell-directed gene transfer abrogates risk of type 1 diabetes development.Molecular therapy. Methods & clinical development · 2022Article
- Role of the PD-1/PD-L1 Dyad in the Maintenance of Pancreatic Immune Tolerance for Prevention of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- Stimulator of interferon genes agonists attenuate type I diabetes progression in NOD mice.Immunology · 2019Article
- Position β57 of I-AScience immunology · 2019Article
- An altered CD8Cellular & molecular immunology · 2019Article
- Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers.Scientific reports · 2018Article
- Co-delivery of autoantigen and dexamethasone in incomplete Freund's adjuvant ameliorates experimental autoimmune encephalomyelitis.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- A novel atheroprotective role of MF59-like adjuvant when co-administered with CETP vaccine in rabbit model of atherosclerosis.Iranian journal of basic medical sciences · 2016Article
- CD4 T cell differentiation in type 1 diabetes.Clinical and experimental immunology · 2016Review
- Thioreductase-Containing Epitopes Inhibit the Development of Type 1 Diabetes in the NOD Mouse Model.Frontiers in immunology · 2016Article
- Lack of the protein tyrosine phosphatase PTPN22 strengthens transplant tolerance to pancreatic islets in mice.Diabetologia · 2015Article
- Article
- Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.Nature communications · 2014Article
- MAS-1 adjuvant immunotherapy generates robust Th2 type and regulatory immune responses providing long-term protection from diabetes in late-stage pre-diabetic NOD mice.Autoimmunity · 2014Article
- Targeting the trimolecular complex: the pathway towards type 1 diabetes prevention.Diabetes technology & therapeutics · 2013Article
- MER5101, a novel Aβ1-15:DT conjugate vaccine, generates a robust anti-Aβ antibody response and attenuates Aβ pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Article
- Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisSubcutaneous immunisation with the 9-23 amino acid region of the insulin B chain (B:9-23) in incomplete Freund's adjuvant (IFA) can protect the majority of 4- to 6-week-old prediabetic NOD mice and is currently in clinical trials. Here we analysed the effect of B:9-23/IFA immunisation at later stages of the disease and the underlying mechanisms.
methodsNOD mice were immunised once s.c. with B:9-23/IFA at 5 or 9 weeks of age, or when blood glucose reached 10 mmol/l or higher. Diabetes incidence was followed in addition to variables such as regulatory T cell (Treg) induction, cytokine production (analysed by Elispot) and emergence of pathogenic CD8(+)/NRP-V7(+) cells.
resultsA single B:9-23/IFA immunisation protected the majority of NOD mice at advanced stages of insulitis, but not after blood glucose reached 13.9 mmol/l. It increased Treg numbers and lost its protective effect after IFNgamma or IL-10 neutralisation, but not in the absence of IL-4. CD4(+)CD25(+) and to a lesser extent IFNgamma-producing cells from mice protected by B:9-23/IFA induced tolerance upon transfer into new NOD animals, indicating that a dominant Treg-mediated effect was operational. Reduced numbers of CD8(+)/NRP-V7(+) memory T cells coincided with protection from the disease. CONCLUSIONS/
interpretationProtection from diabetes after B:9-23/IFA immunisation cannot be achieved once diabetes is fully established, but can be achieved at most prediabetic stages of the disease. Protection is mediated by Tregs that require IFNgamma and IL-10. These findings should provide important guidance for ongoing human trials, especially for the development of suitable T cell biomarkers.
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