ArticleImmunity2012
A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self.
Article in Immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
123 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Regulatory T Cell in Active Systemic Lupus Erythematosus Patients: A Systemic Review and Meta-Analysis.Frontiers in immunology · 2019Pooled it
- Unbiased recording and identification of thymic cellular interactomes using synthetic Notch receptors.Nature communications · 2026Article
- Dual T cell receptor expression provides intrinsic advantage for agonist selection of thymic FoxP3+ regulatory T cells (Tregs) in the neonatal thymus.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Isolation of Pure Stable Human Treg Cells Based on Expression of GPA33.European journal of immunology · 2026Article
- Regulatory T Cell Heterogeneity in the Steady State and Tumor.Immune network · 2026Review
- Striking a balance: how the gut microbiome shapes the fate of intestinal CD4+ T cells.Discovery immunology · 2026Review
- A Novel Approach of T Cell Receptor Classification Reveals Dynamic Interactions Amongst Diet, Microbiota, and Host T Cells.Immune network · 2025Review
- It's Time to Unite: Diversity and Coordination of Thymic Stromal Cells for T Cell Selection and Organ Integrity.Immunological reviews · 2025Review
- A hierarchy of intestinal antigens instructs the CD4Immunity · 2025Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.Development (Cambridge, England) · 2024Article
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function.Cells · 2024Review
- Convergence, plasticity, and tissue residence of regulatory T cell response via TCR repertoire prism.eLife · 2024Article
- Ferritin heavy chain supports stability and function of the regulatory T cell lineage.The EMBO journal · 2024Article
- Cbl-b mitigates the responsiveness of naive CD8Science signaling · 2024Article
- A guide to thymic selection of T cells.Nature reviews. Immunology · 2024Review
- Decoding mutational hotspots in human disease through the gene modules governing thymic regulatory T cells.Frontiers in immunology · 2024Article
- Relationship between Hypoxic and Immune Pathways Activation in the Progression of Neuroinflammation: Role of HIF-1α and Th17 Cells.International journal of molecular sciences · 2023Review
- MHC Class II Presentation in Autoimmunity.Cells · 2023Review
63 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
Abstract
The degree of T cell self-reactivity considered dangerous by the immune system, thereby requiring thymic selection processes to prevent autoimmunity, is unknown. Here, we analyzed a panel of T cell receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA(323-339)) in the rat insulin promoter (RIP)-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T (Treg) cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad ~1,000-fold range. Interestingly, higher TCR affinity was associated with a larger Treg cell developmental "niche" size, even though the amount of antigen should remain constant. The TCR-reactivity threshold to elicit thymic negative selection and peripheral T cell responses was ~100-fold higher than that of Treg cell differentiation. Thus, these data suggest that the broad range of self-reactivity that elicits thymic Treg cell generation is tuned to secure peripheral tolerance to self.
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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.