ArticleDiabetes2011
Uncoupling of proliferation and cytokines from suppression within the CD4+CD25+Foxp3+ T-cell compartment in the 1st year of human type 1 diabetes.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effect of vitamin D3 supplementation on systemic inflammation and disease-specific markers in patients with autoimmune diseases: a comprehensive meta-analysis of randomized controlled trials.Inflammopharmacology · 2026Pooled it
- Increased Plasma Soluble Interleukin-2 Receptor Alpha Levels in Patients With Long-Term Type 1 Diabetes With Vascular Complications Associated WithFrontiers in endocrinology · 2020Article
- Memory T Cells in Type 1 Diabetes: the Devil is in the Detail.Current diabetes reports · 2017Review
- A pilot study showing associations between frequency of CD4(+) memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes.Clinical immunology (Orlando, Fla.) · 2016Article
- Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes.Stem cells (Dayton, Ohio) · 2016Review
- Analyses of regulatory CD4+ CD25+ FOXP3+ T cells and observations from peripheral T cell subpopulation markers during the development of type 1 diabetes in children.Scandinavian journal of immunology · 2016Article
- Article
- Expression of PD-1 Molecule on Regulatory T Lymphocytes in Patients with Insulin-Dependent Diabetes Mellitus.International journal of molecular sciences · 2015Article
- Preterm cord blood CD4⁺ T cells exhibit increased IL-6 production in chorioamnionitis and decreased CD4⁺ T cells in bronchopulmonary dysplasia.Human immunology · 2015Article
- Alteration of regulatory T cells in type 1 diabetes mellitus: a comprehensive review.Clinical reviews in allergy & immunology · 2014Review
- Interindividual variation in human T regulatory cells.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Targeting regulatory T cells in the treatment of type 1 diabetes mellitus.Current molecular medicine · 2012Review
- TH17 Cells in Autoimmunity and Immunodeficiency: Protective or Pathogenic?Frontiers in immunology · 2012Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
objectiveThe mechanistic basis for the breakdown of T-cell tolerance in type 1 diabetes is unclear and could result from a gain of effector function and/or loss of regulatory function. In humans, the CD4+CD25+Foxp3+ T-cell compartment contains both effector and regulatory T cells, and it is not known how their relative proportions vary in disease states. RESEARCH DESIGN AND
methodsWe performed a longitudinal study of CD4+CD25+ T-cell function in children with type 1 diabetes at onset and throughout the 1st year of disease. Function was assessed using single-cell assays of proliferation, cytokine production, and suppression. Type 1 diabetic individuals were compared with age-matched control subjects, and suppression was directly assessed by coculture with control T-cell targets.
resultsWe identify novel functional changes within the type 1 diabetes CD4+CD25+ compartment. Type 1 diabetic CD4+CD25+ cells exhibited a striking increase in proliferative capacity in coculture with CD4 T cells that was present at onset and stable 9-12 months from diagnosis. Elevated type 1 diabetes CD4+CD25+ cell proliferation correlated with increased inflammatory cytokines interleukin 17 and tumor necrosis factor-α but not γ-interferon. Type 1 diabetes CD4+CD25+ cytokine production occurred coincident with suppression of the same cytokines in the control targets. Indeed, enhanced proliferation/cytokines by CD4+CD25+ cells was uncoupled from their suppressive ability. Longitudinally, we observed a transient defect in type 1 diabetes CD4+CD25+ suppression that unexpectedly correlated with measures of improved metabolic function.
conclusionsType 1 diabetes onset, and its subsequent remission period, is associated with two independent functional changes within the CD4+CD25+ T-cell compartment: a stable increase in effector function and a transient decrease in regulatory T-cell suppression.
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