Trial reportJournal of immunology (Baltimore, Md. : 1950)2012
Type 1 diabetes-associated IL2RA variation lowers IL-2 signaling and contributes to diminished CD4+CD25+ regulatory T cell function.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02772679 (A Phase 1 Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy With Interleukin-2 for the Treatment of Type 1 Diabetes), which is not on this map. Cited by 127 papers, 3 of them syntheses 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.
A Phase 1 Trial of CD4+CD127lo/-CD25+ Polyclonal Treg Adoptive Immunotherapy With Interleukin-2 for the Treatment of Type 1 Diabetes
Who cites it
127 citing papers in PubMed, 3 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Association ofFrontiers in immunology · 2025Pooled it
- Association of common polymorphisms in the IL2RA gene with type 1 diabetes: evidence of 32,646 individuals from 10 independent studies.Journal of cellular and molecular medicine · 2015Pooled it
- Pooled it
- IL-2 mutein-engrafted antibody MHS552 selectively expands functional regulatory T cells in nonclinical models and healthy participants.Nature communications · 2026Trial
- Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype.Frontiers in immunology · 2023Trial
- Immune and Metabolic Effects of Antigen-Specific Immunotherapy Using Multiple β-Cell Peptides in Type 1 Diabetes.Diabetes · 2022Trial
- Immunogenicity and safety of HBAI20 Hepatitis B vaccine in non-responders: Double-blinded, randomised, controlled phase 2 trial.Liver international : official journal of the International Association for the Study of the Liver · 2021Trial
- Risk variants disrupting enhancers of TProceedings of the National Academy of Sciences of the United States of America · 2019Trial
- The DILfrequency study is an adaptive trial to identify optimal IL-2 dosing in patients with type 1 diabetes.JCI insight · 2018Trial
- Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial.PLoS medicine · 2016Trial
- Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients.Journal of autoimmunity · 2015Trial
- Immunophenotypic insights into diabetes heterogeneity: The role of CD25-expressing T cells in Ghanaian type 1 diabetes cohorts.Journal of translational autoimmunity · 2026Article
- Article
- Pathogenesis and advances in immunotherapy for type 1 diabetes treatment.Biotechnology reports (Amsterdam, Netherlands) · 2026Review
- ReverseGWAS identifies combined phenotypes associated with a genotype in GWA studies.Bioinformatics (Oxford, England) · 2026Article
- Case Report: IL2RA (CD25) deficiency: first reported cases in Morocco.Frontiers in immunology · 2026Article
- Adapting CAR-T and CAR-Treg cancer therapies for autoimmunity: innovations and challenges.Frontiers in immunology · 2026Review
- Genetic Evidence Implicating Gut Microbiota and Circulating Cytokines in Sjögren's Syndrome.Journal of clinical laboratory analysis · 2026Article
- Explore the key genes and prognosis related to mitochondrial permeability transition driving necrosis gene in kidney renal clear cell carcinoma.Scientific reports · 2025Article
- Genetic Discovery and Risk Prediction for Type 1 Diabetes in Individuals Without High-Risk HLA-DR3/DR4 Haplotypes.Diabetes care · 2025Article
67 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
Numerous reports have demonstrated that CD4(+)CD25(+) regulatory T cells (Tregs) from individuals with a range of human autoimmune diseases, including type 1 diabetes, are deficient in their ability to control autologous proinflammatory responses when compared with nondiseased, control individuals. Treg dysfunction could be a primary, causal event or may result from perturbations in the immune system during disease development. Polymorphisms in genes associated with Treg function, such as IL2RA, confer a higher risk of autoimmune disease. Although this suggests a primary role for defective Tregs in autoimmunity, a link between IL2RA gene polymorphisms and Treg function has not been examined. We addressed this by examining the impact of an IL2RA haplotype associated with type 1 diabetes on Treg fitness and suppressive function. Studies were conducted using healthy human subjects to avoid any confounding effects of disease. We demonstrated that the presence of an autoimmune disease-associated IL2RA haplotype correlates with diminished IL-2 responsiveness in Ag-experienced CD4(+) T cells, as measured by phosphorylation of STAT5a, and is associated with lower levels of FOXP3 expression by Tregs and a reduction in their ability to suppress proliferation of autologous effector T cells. These data offer a rationale that contributes to the molecular and cellular mechanisms through which polymorphisms in the IL-2RA gene affect immune regulation, and consequently upon susceptibility to autoimmune and inflammatory diseases.
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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.