ArticleThe Journal of experimental medicine2003
Restricting Zap70 expression to CD4+CD8+ thymocytes reveals a T cell receptor-dependent proofreading mechanism controlling the completion of positive selection.
Article in The Journal of experimental medicine, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Age-dependent Zap70 expression in thymocytes regulates selection of the neonatal regulatory T cell repertoire.Nature immunology · 2025Article
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Enhancers in T Cell development and malignant lesions.Cell death discovery · 2024Review
- The order and logic of CD4 versus CD8 lineage choice and differentiation in mouse thymus.Nature communications · 2021Article
- Intrathymic adeno-associated virus gene transfer rapidly restores thymic function and long-term persistence of gene-corrected T cells.The Journal of allergy and clinical immunology · 2020Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- Engineering a Dual Small Molecule Gated ZAP70 Switch in T Cells.ACS synthetic biology · 2018Article
- Article
- Histone H3 Lysine 27 demethylases Jmjd3 and Utx are required for T-cell differentiation.Nature communications · 2015Article
- A Zap70-dependent feedback circuit is essential for efficient selection of CD4 lineage thymocytes.Immunology and cell biology · 2015Article
- Quantitative and temporal requirements revealed for Zap70 catalytic activity during T cell development.Nature immunology · 2014Article
- Overlapping and asymmetric functions of TCR signaling during thymic selection of CD4 and CD8 lineages.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- A ZAP-70 kinase domain variant prevents thymocyte-positive selection despite signalling CD69 induction.Immunology · 2014Article
- Theories and quantification of thymic selection.Frontiers in immunology · 2014Review
- Thpok-independent repression of Runx3 by Gata3 during CD4+ T-cell differentiation in the thymus.European journal of immunology · 2013Article
- Article
- LKB1 regulates TCR-mediated PLCγ1 activation and thymocyte positive selection.The EMBO journal · 2011Article
- The enigma of CD4-lineage specification.European journal of immunology · 2011Review
- Decision checkpoints in the thymus.Nature immunology · 2010Review
- The transcription factor Ets1 is important for CD4 repression and Runx3 up-regulation during CD8 T cell differentiation in the thymus.The Journal of experimental medicine · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Although T cell receptor (TCR) signals are essential for intrathymic T cell-positive selection, it remains controversial whether they only serve to initiate this process, or whether they are required throughout to promote thymocyte differentiation and survival. To address this issue, we have devised a novel approach to interfere with thymocyte TCR signaling in a developmental stage-specific manner in vivo. We have reconstituted mice deficient for Zap70, a tyrosine kinase required for TCR signaling and normally expressed throughout T cell development, with a Zap70 transgene driven by the adenosine deaminase (ADA) gene enhancer, which is active in CD4(+)CD8(+) thymocytes but inactive in CD4(+) or CD8(+) single-positive (SP) thymocytes. In such mice, termination of Zap70 expression impaired TCR signal transduction and arrested thymocyte development after the initiation, but before the completion, of positive selection. Arrested thymocytes had terminated Rag gene expression and up-regulated TCR and Bcl-2 expression, but failed to differentiate into mature CD4 or CD8 SP thymocytes, to be rescued from death by neglect or to sustain interleukin 7R alpha expression. These observations identify a TCR-dependent proofreading mechanism that verifies thymocyte TCR specificity and differentiation choices before the completion of positive selection.
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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.