ArticleClinical and experimental immunology2015
Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model.
Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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
35 citing papers in PubMed, 55 citations in OpenAlex.
- Immune and Metabolic Effects of Antigen-Specific Immunotherapy Using Multiple β-Cell Peptides in Type 1 Diabetes.Diabetes · 2022Trial
- The central role of the β-cell in diabetes: from monogenic forms to type 1, type 2, and gestational diabetes.Reviews in endocrine & metabolic disorders · 2026Review
- Preclinical development and clinical safety assessment of a synthetic peptide conjugate enabling endogenous antibody binding to promote innate receptor engagement.Molecular therapy. Oncology · 2025Article
- New Perspectives in Studying Type 1 Diabetes Susceptibility Biomarkers.International journal of molecular sciences · 2025Review
- Article
- Immunotherapy in type 1 diabetes: Novel pathway to the future ahead.World journal of diabetes · 2024Article
- Tolerogenic dendritic cells in type 1 diabetes: no longer a concept.Frontiers in immunology · 2023Review
- The need and benefit of immune monitoring to define patient and disease heterogeneity, mechanisms of therapeutic action and efficacy of intervention therapy for precision medicine in type 1 diabetes.Frontiers in immunology · 2023Article
- Dendritic Cells and Their Immunotherapeutic Potential for Treating Type 1 Diabetes.International journal of molecular sciences · 2022Review
- Article
- From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes.Frontiers in medicine · 2022Review
- Tolerogenic dendritic cells pulsed with islet antigen induce long-term reduction in T-cell autoreactivity in type 1 diabetes patients.Frontiers in immunology · 2022Article
- Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes.Frontiers in endocrinology · 2022Review
- Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1.International journal of molecular sciences · 2021Review
- 100 Years of Insulin: Lifesaver, immune target, and potential remedy for prevention.Med (New York, N.Y.) · 2021Review
- Current advances in using tolerogenic dendritic cells as a therapeutic alternative in the treatment of type 1 diabetes.World journal of diabetes · 2021Review
- Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?).Nature reviews. Endocrinology · 2021Review
- A Question of Tolerance-Antigen-Specific Immunotherapy for Type 1 Diabetes.Current diabetes reports · 2020Review
- Therapeutic administration of Tregitope-Human Albumin Fusion with Insulin Peptides to promote Antigen-Specific Adaptive Tolerance Induction.Scientific reports · 2019Article
- Combination peptide immunotherapy suppresses antibody and helper T-cell responses to the major human platelet autoantigen glycoprotein IIb/IIIa in HLA-transgenic mice.Haematologica · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses, including proinsulin-specific T cell proliferation, interferon (IFN)-γ and autoantibody production. These are preventable and quenchable by pre- and post-induction treatment, respectively, using intradermal proinsulin-PIT injections. Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box protein 3 (FoxP3(+))CD25(high) ] CD4 T cells, including those capable of proinsulin-specific regulation, suggesting this as its main mode of action. In contrast, peptide delivered intradermally on the surface of vitamin D3-modulated (tolerogenic) dendritic cells, controls autoimmunity in association with proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells. These studies define a humanized, translational model for in vivo optimization of PIT to control autoimmunity in type 1 diabetes and indicate that dominant mechanisms of action differ according to mode of peptide delivery.
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.