ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Thymic medullary epithelium and thymocyte self-tolerance require cooperation between CD28-CD80/86 and CD40-CD40L costimulatory pathways.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Thymic Crosstalk: An Overview of the Complex Cellular Interactions that Control the Establishment of T-Cell Tolerance.Advances in experimental medicine and biology · 2025Review
- Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection.Frontiers in immunology · 2024Article
- Article
- Antigen-presenting T cells provide critical B7 co-stimulation for thymic iNKT cell development via CD28-dependent trogocytosis.Cell reports · 2022Article
- Type 2 cytokines in the thymus activate SirpαNature immunology · 2022Article
- The ICOS-ICOSL pathway tunes thymic selection.Immunology and cell biology · 2022Article
- Transcriptional and epigenetic regulation in thymic epithelial cells.Immunological reviews · 2022Review
- Dual roles for LUBAC signaling in thymic epithelial cell development and survival.Cell death and differentiation · 2021Article
- Lymphotoxin: from the physiology to the regeneration of the thymic function.Cell death and differentiation · 2021Review
- Comprehensive genomic and immunophenotypic analysis of CD4 T cell infiltrating human triple-negative breast cancer.Cancer immunology, immunotherapy : CII · 2021Article
- Novel Combination of Surface Markers for the Reliable and Comprehensive Identification of Human Thymic Epithelial Cells by Flow Cytometry: Quantitation and Transcriptional Characterization of Thymic Stroma in a Pediatric Cohort.Frontiers in immunology · 2021Article
- Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells.Nature communications · 2020Article
- Inducers, Attractors and Modulators of CD4Frontiers in immunology · 2020Review
- Exosomes derived from statin-modified bone marrow dendritic cells increase thymus-derived natural regulatory T cells in experimental autoimmune myasthenia gravis.Journal of neuroinflammation · 2019Article
- Medullary thymic epithelial NF-kB-inducing kinase (NIK)/IKKα pathway shapes autoimmunity and liver and lung homeostasis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Measuring Thymic Clonal Deletion at the Population Level.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- LKB1 expressed in dendritic cells governs the development and expansion of thymus-derived regulatory T cells.Cell research · 2019Article
- Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice.Communications biology · 2019Article
- Twenty Years of AIRE.Frontiers in immunology · 2018Review
- Cultured Human Thymic-Derived Cells Display Medullary Thymic Epithelial Cell Phenotype and Functionality.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
A critical process during thymic development of the T cell repertoire is the induction of self-tolerance. Tolerance in developing T cells is highly dependent on medullary thymic epithelial cells (mTEC), and mTEC development in turn requires signals from mature single-positive thymocytes, a bidirectional relationship termed thymus crosstalk. We show that CD28-CD80/86 and CD40-CD40L costimulatory interactions, which mediate negative selection and self-tolerance, upregulate expression of LTα, LTβ, and receptor activator for NF-κB in the thymus and are necessary for medullary development. Combined absence of CD28-CD80/86 and CD40-CD40L results in profound deficiency in mTEC development comparable to that observed in the absence of single-positive thymocytes. This requirement for costimulatory signaling is maintained even in a TCR transgenic model of high-affinity TCR-ligand interactions. CD4 thymocytes maturing in the altered thymic epithelial environment of CD40/CD80/86 knockout mice are highly autoreactive in vitro and are lethal in congenic adoptive transfer in vivo, demonstrating a critical role for these costimulatory pathways in self-tolerance as well as thymic epithelial development. These findings demonstrate that cooperativity between CD28-CD80/86 and CD40-CD40L pathways is required for normal medullary epithelium and for maintenance of self-tolerance in thymocyte development.
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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.