ArticleThe Journal of experimental medicine2002
Failure to censor forbidden clones of CD4 T cells in autoimmune diabetes.
Article in The Journal of experimental medicine, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 136 citations in OpenAlex.
- Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity.iScience · 2023Article
- Evidence of genetic epistasis in autoimmune diabetes susceptibility revealed by mouse congenic sublines.Immunogenetics · 2021Article
- DOCK8 deficiency diminishes thymic T-regulatory cell development but not thymic deletion.Clinical & translational immunology · 2021Article
- Haploidentical mixed chimerism cures autoimmunity in established type 1 diabetic mice.The Journal of clinical investigation · 2020Article
- Type 1 diabetes pathogenesis and the role of inhibitory receptors in islet tolerance.Annals of the New York Academy of Sciences · 2020Review
- Genetic interaction between two insulin-dependent diabetes susceptibility loci, Idd2 and Idd13, in determining immunoregulatory DN T cell proportion.Immunogenetics · 2018Article
- An orthologous non-MHC locus in rats and mice is linked to CD4Genes and immunity · 2017Article
- High-level intrathymic thyrotrophin receptor expression in thyroiditis-prone mice protects against the spontaneous generation of pathogenic thyrotrophin receptor autoantibodies.Clinical and experimental immunology · 2017Article
- Spontaneous germinal centers and autoimmunity.Autoimmunity · 2017Review
- Beta-cell Specific Autoantibodies: Are they Just an Indicator of Type 1 Diabetes?Current diabetes reviews · 2017Review
- TCR transgenic mice reveal the impact of type 1 diabetes loci on early and late disease checkpoints.Immunology and cell biology · 2016Article
- Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes.Nature genetics · 2016Article
- Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.Immunologic research · 2016Review
- Mechanisms of diabetic autoimmunity: II--Is diabetes a central or peripheral disorder of effector and regulatory cells?Immunologic research · 2016Review
- Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-A(k) NOD mice.Genes and immunity · 2015Article
- Quantitative reduction of the TCR adapter protein SLP-76 unbalances immunity and immune regulation.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Single-cell mass cytometry of TCR signaling: amplification of small initial differences results in low ERK activation in NOD mice.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Idd13 is involved in determining immunoregulatory DN T-cell number in NOD mice.Genes and immunity · 2014Article
- CD8+ dendritic cell-mediated tolerance of autoreactive CD4+ T cells is deficient in NOD mice and can be corrected by blocking CD40L.Journal of leukocyte biology · 2014Article
- Thyroid disorders associated with alopecia areata in egyptian patients.Indian journal of dermatology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes and other organ-specific autoimmune diseases often cluster together in human families and in congenic strains of NOD (nonobese diabetic) mice, but the inherited immunoregulatory defects responsible for these diseases are unknown. Here we track the fate of high avidity CD4 T cells recognizing a self-antigen expressed in pancreatic islet beta cells using a transgenic mouse model. T cells of identical specificity, recognizing a dominant peptide from the same islet antigen and major histocompatibility complex (MHC)-presenting molecule, were followed on autoimmune susceptible and resistant genetic backgrounds. We show that non-MHC genes from the NOD strain cause a failure to delete these high avidity autoreactive T cells during their development in the thymus, with subsequent spontaneous breakdown of CD4 cell tolerance to the islet antigen, formation of intra-islet germinal centers, and high titre immunoglobulin G1 autoantibody production. In mixed bone marrow chimeric animals, defective thymic deletion was intrinsic to T cells carrying diabetes susceptibility genes. These results demonstrate a primary failure to censor forbidden clones of self-reactive T cells in inherited susceptibility to organ-specific autoimmune disease, and highlight the importance of thymic mechanisms of tolerance in organ-specific tolerance.
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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.