ArticleProceedings of the National Academy of Sciences of the United States of America2008
The defect in T-cell regulation in NOD mice is an effect on the T-cell effectors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
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Who cites it
108 citing papers in PubMed, 190 citations in OpenAlex.
- Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children.Diabetes care · 2012Trial
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- Lactococcus lactis-HSP65 requires TLR2 to induce tolerogenic dendritic cells and confer protection against type 1 diabetes in a murine model.Cellular and molecular life sciences : CMLS · 2025Article
- Type 1 Diabetes: A Guide to Autoimmune Mechanisms for Clinicians.Diabetes, obesity & metabolism · 2025Review
- The type 1 diabetes susceptibility locusFrontiers in immunology · 2024Article
- Mouse models of preeclampsia with preexisting comorbidities.Frontiers in physiology · 2023Review
- The long and winding road: From mouse linkage studies to a novel human therapeutic pathway in type 1 diabetes.Frontiers in immunology · 2022Review
- Enhanced CD4Scientific reports · 2021Article
- Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.Cell reports · 2021Article
- Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes.Diabetologia · 2021Article
- Prenatal cadmium exposure does not induce greater incidence or earlier onset of autoimmunity in the offspring.PloS one · 2021Article
- Haploidentical mixed chimerism cures autoimmunity in established type 1 diabetic mice.The Journal of clinical investigation · 2020Article
- CD70 Inversely Regulates Regulatory T Cells and Invariant NKT Cells and Modulates Type 1 Diabetes in NOD Mice.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- The Role of T Cell Receptor Signaling in the Development of Type 1 Diabetes.Frontiers in immunology · 2020Review
- Trisomy 21 dysregulates T cell lineages toward an autoimmunity-prone state associated with interferon hyperactivity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Next-generation regulatory T cell therapy.Nature reviews. Drug discovery · 2019Review
- Article
- Genetic and functional data identifying Cd101 as a type 1 diabetes (T1D) susceptibility gene in nonobese diabetic (NOD) mice.PLoS genetics · 2019Article
- Hyaluronan in immune dysregulation and autoimmune diseases.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
48 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
7 authors at 4 institutions in 1 country.
Funding
Abstract
FoxP3(+) regulatory T cells (Tregs) protect against autoimmunity, type 1 diabetes (T1D) in particular, prompting the hypothesis that a deficiency in Tregs is a critical determinant of diabetes susceptibility in NOD mice. However, tests of this hypothesis have yielded contradictory results. We confirmed that NOD mice, compared with reference strains, do not have a primary deficit in Treg numbers in the lymphoid organs, whether in prediabetic mice of any age or in animals with recent-onset diabetes. NOD Tregs did show a defect in standard in vitro T cell suppression assays, particularly at low suppressor/effector ratios. Gene expression profiling revealed the vast majority of transcripts constituting the "Treg signature" to be normally distributed in NOD Tregs versus CD4(+) T conventional (Tconv) cells, although there were a few differences affecting one or the other population. According to results from criss-cross experiments, the functional inefficacy was not rooted in NOD Tregs, which suppressed as well as their C57BL/6 (B6) counterparts, but rather in NOD Tconv, which were less prone to suppression than were B6 Tconv cells. They also responded more effectively to anti-CD3/28 monoclonal antibody (mAb) stimulation in vitro or to a natural pancreatic antigen in vivo. This difference was independent of autoimmune inflammation, did not map to the idd3 region, and was not due to the overproduction of interleukin-21 in NOD mice. That the immune dysregulation in this T1D model is rooted in the ability of effector T cells to be regulated, rather than in Tregs themselves, has implications for proposed therapeutic interventions.
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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.