ArticleClinical & translational immunology2016
Treg activation defect in type 1 diabetes: correction with TNFR2 agonism.
Article in Clinical & translational immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Single-cell transcriptome landscape of circulating CD4Cell genomics · 2024Pooled it
- Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study.Frontiers in immunology · 2020Trial
- Double activation and low IL-2 manufacturing protocol increase expansion of healthy and patient-derived CAR-Tregs.Molecular therapy. Advances · 2026Article
- Review
- Regulatory T cells in cancer and inflammation.Signal transduction and targeted therapy · 2026Review
- Constitutively Active Stat5b Expression in Dendritic Cells Enhances Treg-Mediated Elimination of Autoreactive CD8International journal of molecular sciences · 2026Article
- Decoding Treg diversity and dysfunction to advance Treg-based therapies in autoimmune and inflammatory diseases.Frontiers in immunology · 2026Review
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- TNFR2 Agonism: Basic Science and Promising Treatment for Multiple Sclerosis and Related Diseases.International journal of molecular sciences · 2025Review
- Advances in Regulatory Cell Therapy for Type 1 Diabetes: Emerging Strategies and Future Directions.European journal of immunology · 2025Review
- Tumor necrosis factor receptor 2 in allergen tolerance: a perspective view.Frontiers in immunology · 2025Review
- Bronchial anastomotic complications as a microvascular disruption in a mouse model of airway transplantation.Frontiers in immunology · 2025Review
- Regulatory T cell dysfunction and immunotherapeutic breakthroughs in type 1 diabetes.Frontiers in endocrinology · 2025Review
- Regulatory T Cell Dysfunction in Autoimmune Diseases.International journal of molecular sciences · 2024Review
- Potential clinical implications of molecular mimicry-induced autoimmunity.Immunity, inflammation and disease · 2024Review
- CAR-engineered T cell therapy as an emerging strategy for treating autoimmune diseases.Frontiers in medicine · 2024Review
- Insulin-like Growth Factor-1 Synergizes with IL-2 to Induce Homeostatic Proliferation of Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Development of a 1:1-binding biparatopic anti-TNFR2 antagonist by reducing signaling activity through epitope selection.Communications biology · 2023Article
- Investigating immune profile by CyTOF in individuals with long-standing type 1 diabetes.Scientific reports · 2023Article
- BCG Vaccination and the Risk of Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Pathogens (Basel, Switzerland) · 2023Review
4 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
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activated T-regulatory cells (aTregs) prevent or halt various forms of autoimmunity. We show that type 1 diabetics (T1D) have a Treg activation defect through an increase in resting Tregs (rTregs, CD4(+)CD25(+)Foxp3(+)CD45RA) and decrease in aTregs (CD4(+)CD25(+)Foxp3(+)CD45RO) (n= 55 T1D, n=45 controls, P=0.01). The activation defect persists life long in T1D subjects (T1D=45, controls=45, P=0.01, P=0.04). Lower numbers of aTregs had clinical significance because they were associated with a trend for less residual C-peptide secretion from the pancreas (P=0.08), and poorer HbA1C control (P=0.03). In humans, the tumor necrosis factor receptor 2 (TNFR2) is obligatory for Treg induction, maintenance and expansion of aTregs. TNFR2 agonism is a method for stimulating Treg conversion from resting to activated. Using two separate in vitro expansion protocols, TNFR2 agonism corrected the T1D activation defect by triggering conversion of rTregs into aTregs (n=54 T1D, P<0.001). TNFR2 agonism was superior to standard protocols and TNF in proliferating Tregs. In T1D, TNFR2 agonist-expanded Tregs were homogeneous and functionally potent by virtue of suppressing autologous cytotoxic T cells in a dose-dependent manner comparable to controls. Targeting the TNFR2 receptor for Treg expansion in vitro demonstrates a means to correct the activation defect in T1D.
Identifiers
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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.