ArticlePLoS biology2013
Elimination of self-reactive T cells in the thymus: a timeline for negative selection.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Design principles for integrated AI alignment.Patterns (New York, N.Y.) · 2026Review
- Early-life thymectomy results in visceral adipose tissue inflammation and glucose intolerance.Immunity & ageing : I & A · 2025Article
- Basic interactions responsible for thymus function explain the convoluted medulla shape.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- Early life thymectomy induces arterial dysfunction in mice.GeroScience · 2024Article
- Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis.Frontiers in immunology · 2024Review
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- THEMIS increases TCR signaling in CD4Science signaling · 2023Article
- A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.Nature immunology · 2023Article
- MNT suppresses T cell apoptosis via BIM and is critical for T lymphomagenesis.Cell death and differentiation · 2023Article
- Fetal Thymic Organ Culture and Negative Selection.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Studying T Cell Development in Neonatal and Adult Thymic Slices.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The ICOS-ICOSL pathway tunes thymic selection.Immunology and cell biology · 2022Article
- The TAM receptor tyrosine kinases Axl and Mer drive the maintenance of highly phagocytic macrophages.Frontiers in immunology · 2022Article
- Targeting TGF-β signaling in the multiple myeloma microenvironment: Steering CARs and T cells in the right direction.Frontiers in cell and developmental biology · 2022Review
- T cell self-reactivity during thymic development dictates the timing of positive selection.eLife · 2021Article
- Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes.Mucosal immunology · 2021Article
- Liver X receptors are required for thymic resilience and T cell output.The Journal of experimental medicine · 2020Article
- In situ neutrophil efferocytosis shapes T cell immunity to influenza infection.Nature immunology · 2020Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
The elimination of autoreactive T cells occurs via thymocyte apoptosis and removal by thymic phagocytes, but the sequence of events in vivo, and the relationship between thymocyte death and phagocytic clearance, are unknown. Here we address these questions by following a synchronized cohort of thymocytes undergoing negative selection within a three-dimensional thymic tissue environment, from the initial encounter with a negative selecting ligand to thymocyte death and clearance. Encounter with cognate peptide-MHC complexes results in rapid calcium flux and migratory arrest in auto-reactive thymocytes over a broad range of peptide concentrations, followed by a lag period in which gene expression changes occurred, but there was little sign of thymocyte death. Caspase 3 activation and thymocyte loss were first detectable at 2 and 3 hours, respectively, and entry of individual thymocytes into the death program occurred asynchronously over the next 10 hours. Two-photon time-lapse imaging revealed that thymocyte death and phagocytosis occurred simultaneously, often with thymocytes engulfed prior to changes in chromatin and membrane permeability. Our data provide a timeline for negative selection and reveal close coupling between cell death and clearance in the thymus.
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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.