ArticleProceedings of the National Academy of Sciences of the United States of America2013
An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 110 citations in OpenAlex.
- Semaphorins: from CD8⁺ T cells to cancer immunotherapy.Biomarker research · 2026Review
- A centrally positioned cluster of multiple centrioles in antigen-presenting cells fosters T cell activation.Nature communications · 2026Article
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
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- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- Cytosolic protein translation regulates cell asymmetry and function in early TCR activation of human CD8Frontiers in immunology · 2024Article
- Evolutionary design of explainable algorithms for biomedical image segmentation.Nature communications · 2023Article
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- Bioactive Constituents ofInternational journal of molecular sciences · 2023Article
- Lytic granule exocytosis at immune synapses: lessons from neuronal synapses.Frontiers in immunology · 2023Review
- Measuring CTL Lytic Granule Secretion and Target Cell Membrane Repair by Fluorescent Lipophilic Dye Uptake at the Lytic Synapse.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Tumour immunotherapy: lessons from predator-prey theory.Nature reviews. Immunology · 2022Review
- Learning from TCR Signaling and Immunological Synapse Assembly to Build New Chimeric Antigen Receptors (CARs).International journal of molecular sciences · 2022Review
- Mechanically active integrins target lytic secretion at the immune synapse to facilitate cellular cytotoxicity.Nature communications · 2022Article
- Stochastic model of T cell repolarization during target elimination (II).Biophysical journal · 2022Article
- Cell polarity regulators, multifunctional organizers of lymphocyte activation and function.Biomedical journal · 2022Review
- Ultrarapid lytic granule release from CTLs activates CaScience advances · 2022Article
- ALFA-PRF: a novel approach to detect murine perforin release from CTLs into the immune synapse.Frontiers in immunology · 2022Article
- Review
- The Expanding Arsenal of Cytotoxic T Cells.Frontiers in immunology · 2022Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is presently assumed that lethal hit delivery by cytotoxic T lymphocytes (CTLs) is mechanistically linked to centrosome polarization toward target cells, leading to dedicated release of lytic granules within a confined secretory domain. Here we provide three lines of evidence showing that this mechanism might not apply as a general paradigm for lethal hit delivery. First, in CTLs stimulated with immobilized peptide-MHC complexes, lytic granules and microtubule organizing center localization into synaptic areas are spatio-temporally dissociated, as detected by total internal reflection fluorescence microscopy. Second, in many CTL/target cell conjugates, lytic granule secretion precedes microtubule polarization and can be detected during the first minute after cell-cell contact. Third, inhibition of microtubule organizing center and centrosome polarization impairs neither lytic granule release at the CTL synapse nor killing efficiency. Our results broaden current views of CTL biology by revealing an extremely rapid step of lytic granule secretion and by showing that microtubule organizing center polarization is dispensable for efficient lethal hit delivery.
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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.