ArticleThe Journal of biological chemistry2013
Vav1-phospholipase C-γ1 (Vav1-PLC-γ1) pathway initiated by T cell antigen receptor (TCRγδ) activation is required to overcome inhibition by ubiquitin ligase Cbl-b during γδT cell cytotoxicity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Immunophenotypic Profiling of Lymphocyte Subsets in Children and Adolescents With Acute Lymphoblastic Leukaemia: Immune Dysregulation Before and After Remission.Journal of immunology research · 2026Article
- The mechanism regulating the cytotoxicity of γδ T cells activated by mycobacterium tuberculosis heat-resistant antigen based on RNA-seq analysis.Frontiers in immunology · 2026Article
- Graft-versus-Host Disease Modulation by Innate T Cells.International journal of molecular sciences · 2023Review
- γδ T cells as a potential therapeutic agent for glioblastoma.Frontiers in immunology · 2023Review
- Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Circulating CD56+ NKG2D+ NK cells and postoperative fertility in ovarian endometrioma.Scientific reports · 2020Article
- miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity.Cellular & molecular immunology · 2019Article
- The complex existence of γδ T cells following transplantation: the good, the bad and the simply confusing.Clinical & translational immunology · 2019Review
- Characteristics of Peripheral Immune Function in Reproductive Females with Uterine Leiomyoma.Journal of oncology · 2019Article
- Salp15, a Multifunctional Protein From Tick Saliva With Potential Pharmaceutical Effects.Frontiers in immunology · 2019Review
- γδ T Cells in Peripheral Blood of Glioma Patients.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias.Frontiers in immunology · 2018Review
- Exoenzyme T Plays a Pivotal Role in the IFN-γ Production afterFrontiers in immunology · 2017Article
- Human γδ T cells augment antigen presentation inMolecular medicine (Cambridge, Mass.) · 2016Article
- Assay of Peripheral Regulatory Vδ1 T Cells in Ankylosing Spondylitis and its Significance.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Article
- The promise of γδ T cells and the γδ T cell receptor for cancer immunotherapy.Cellular & molecular immunology · 2015Review
- Hyperactivation and in situ recruitment of inflammatory Vδ2 T cells contributes to disease pathogenesis in systemic lupus erythematosus.Scientific reports · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T cell antigen receptor γδ (TCRγδ) and natural killer group 2, member D (NKG2D) are two crucial receptors for γδT cell cytotoxicity. Compelling evidences suggest that γδT cell cytotoxicity is TCRγδ-dependent and can be co-stimulated by NKG2D. However, the molecular mechanism of underlying TCRγδ-dependent activation of γδT cells remains unclear. In this study we demonstrated that TCRγδ but not NKG2D engagement induced lytic granule polarization and promoted γδT cell cytotoxicity. TCRγδ activation alone was sufficient to trigger Vav1-dependent phospholipase C-γ1 signaling, resulting in lytic granule polarization and effective killing, whereas NKG2D engagement alone failed to trigger cytotoxicity-related signaling to overcome the inhibitory effect of Cbl-b; therefore, NKG2D engagement alone could not induce effective killing. However, NKG2D ligation augmented the activation of γδT cell cytotoxicity through the Vav1-phospholipase C-γ1 pathway. Vav1 overexpression or Cbl-b knockdown not only enhanced TCRγδ activation-initiated killing but also enabled NKG2D activation alone to induce γδT cell cytotoxicity. Taken together, our results suggest that the activation of γδT cell cytotoxicity requires a strong activation signal to overcome the inhibitory effect of Cbl-b. Our finding provides new insights into the molecular mechanisms underlying the initiation of γδT cell cytotoxicity and likely implications for optimizing γδT cell-based cancer immunotherapy.
Indexed as
Identifiers
What OpenQuestion holds
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.