ArticleThe Journal of experimental medicine2012
Thymic negative selection is functional in NOD mice.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice.The Journal of clinical investigation · 2024Article
- Crinophagic granules in pancreatic β cells contribute to mouse autoimmune diabetes by diversifying pathogenic epitope repertoire.Nature communications · 2024Article
- NKG2D receptor signaling shapes T cell thymic education.Journal of leukocyte biology · 2024Article
- HLA-DQ8 Supports Development of Insulitis Mediated by Insulin-Reactive Human TCR-Transgenic T Cells in Nonobese Diabetic Mice.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- γδ T cells: origin and fate, subsets, diseases and immunotherapy.Signal transduction and targeted therapy · 2023Review
- Single-cell multiomic analysis of thymocyte development reveals drivers of CD4Nature immunology · 2023Article
- 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
- Genetic Variation in Type 1 Diabetes Reconfigures the 3D Chromatin Organization of T Cells and Alters Gene Expression.Immunity · 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
- 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
- The circadian gene Arntl2 on distal mouse chromosome 6 controls thymocyte apoptosis.Mammalian genome : official journal of the International Mammalian Genome Society · 2017Article
- Type 1 Diabetes: A Chronic Anti-Self-Inflammatory Response.Frontiers in immunology · 2017Review
- Hydrophobic CDR3 residues promote the development of self-reactive T cells.Nature immunology · 2016Article
- Lower Affinity T Cells are Critical Components and Active Participants of the Immune Response.Frontiers in immunology · 2015Review
- Thymic Nurse Cells Participate in Heterotypic Internalization and Repertoire Selection of Immature Thymocytes; Their Removal from the Thymus of Autoimmune Animals May be Important to Disease Etiology.Current molecular medicine · 2015Review
- How Does Thymus Infection by Coxsackievirus Contribute to the Pathogenesis of Type 1 Diabetes?Frontiers in immunology · 2015Review
- Systems biology. Conditional density-based analysis of T cell signaling in single-cell data.Science (New York, N.Y.) · 2014Article
- 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
- Lymphopenia-induced proliferation in aire-deficient mice helps to explain their autoimmunity and differences from human patients.Frontiers in immunology · 2014Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Based on analyses of multiple TCR transgenic (tg) models, the emergence of pathogenic T cells in diabetes-prone NOD mice has been ascribed to a failure to censure autoreactive clones in the thymus. In contrast, using isolated and preselected thymocytes, we show that nonobese diabetic (NOD) genetic variation impairs neither clonal deletion nor downstream transcriptional programs. However, we find that NOD genetic variation influences αβ/γδ-lineage decisions promoted by early expression of tg αβ-TCRs at the double-negative (DN) stage. In B6 and other genetic backgrounds, tg αβ-TCRs behave like γδ-TCRs and commit a large fraction of DNs toward the γδ-lineage, thereby decreasing the size of the double-positive (DP) pool, which is efficiently positively and negatively selected. In NOD DNs, αβ-TCR signalosomes instead behave like pre-TCRs, resulting in high numbers of DPs competing for limited selection niches, and poor positive and negative selection. Once niche effects are neutralized in mixed bone marrow chimeras, positive and negative selection are equally efficient on B6 and NOD backgrounds. Biochemical analysis revealed a selective defect in the activation of Erk1/2 downstream of NOD αβ-TCR signalosomes. Therefore, NOD genetic variation influences αβ/γδ-lineage decisions when the αβ-TCR heterodimer is prematurely expressed, but not the process of negative selection.
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