ArticleProceedings of the National Academy of Sciences of the United States of America2014
Enforcement of γδ-lineage commitment by the pre-T-cell receptor in precursors with weak γδ-TCR signals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- HEB collaborates with TCR signaling to upregulatebioRxiv : the preprint server for biology · 2025Article
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- E proteins control the development of NKγδT cells through their invariant T cell receptor.Nature communications · 2024Article
- γδ T cells: origin and fate, subsets, diseases and immunotherapy.Signal transduction and targeted therapy · 2023Review
- Pre-T cell receptor localization and trafficking are independent of its signaling.The Journal of cell biology · 2023Article
- Distinct subpopulations of DN1 thymocytes exhibit preferential γδ T lineage potential.Frontiers in immunology · 2023Article
- Dietary glucosamine overcomes the defects in αβ-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis.Nature communications · 2022Article
- Direct regulation of TCR rearrangement and expression by E proteins during early T cell development.WIREs mechanisms of disease · 2022Review
- γδ T Cells in Skin Inflammation.Critical reviews in immunology · 2022Review
- Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Gamma Delta T Cells and Their Pathogenic Role in Psoriasis.Frontiers in immunology · 2021Review
- Diagnostic and prognostic value of the peripheral natural killer cell levels in gastric cancer.Experimental and therapeutic medicine · 2020Article
- Metabolic coordination of T cell quiescence and activation.Nature reviews. Immunology · 2020Review
- Efficient CD4Cre-Mediated Conditional KRas Expression in Alveolar Macrophages and Alveolar Epithelial Cells Causes Fatal Hyperproliferative Pneumonitis.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Integration of T-cell receptor, Notch and cytokine signals programs mouse γδ T-cell effector differentiation.Immunology and cell biology · 2018Article
- Metabolic signaling directs the reciprocal lineage decisions of αβ and γδ T cells.Science immunology · 2018Article
- Role of a selecting ligand in shaping the murine γδ-TCR repertoire.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- HEB is required for the specification of fetal IL-17-producing γδ T cells.Nature communications · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Developing thymocytes bifurcate from a bipotent precursor into αβ- or γδ-lineage T cells. Considering this common origin and the fact that the T-cell receptor (TCR) β-, γ-, and δ-chains simultaneously rearrange at the double negative (DN) stage of development, the possibility exists that a given DN cell can express and transmit signals through both the pre-TCR and γδ-TCR. Here, we tested this scenario by defining the differentiation outcomes and criteria for lineage choice when both TCR-β and γδ-TCR are simultaneously expressed in Rag2(-/-) DN cells via retroviral transduction. Our results showed that Rag2(-/-) DN cells expressing both TCRs developed along the γδ-lineage, down-regulated CD24 expression, and up-regulated CD73 expression, showed a γδ-biased gene-expression profile, and produced IFN-γ in response to stimulation. However, in the absence of Inhibitor of DNA-binding 3 expression and strong γδ-TCR ligand, γδ-expressing cells showed a lower propensity to differentiate along the γδ-lineage. Importantly, differentiation along the γδ-lineage was restored by pre-TCR coexpression, which induced greater down-regulation of CD24, higher levels of CD73, Nr4a2, and Rgs1, and recovery of functional competence to produce IFN-γ. These results confirm a requirement for a strong γδ-TCR ligand engagement to promote maturation along the γδ T-cell lineage, whereas additional signals from the pre-TCR can serve to enforce a γδ-lineage choice in the case of weaker γδ-TCR signals. Taken together, these findings further cement the view that the cumulative signal strength sensed by developing DN cells serves to dictate its lineage choice.
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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.