Apoptotic contraction drives target cell release by cytotoxic T cells Research Letter
| Authors: | Sanchez, E. E.; Tello-Lafoz, M.; Guo, A. J.; de Jesus, M.; Elbanna, Y. A.; Winer, B. Y.; Budhu, S.; Chan, E.; Rosiek, E.; Kondo, T.; DuSold, J.; Taylor, N.; Altan-Bonnet, G.; Olson, M. F.; Huse, M. |
| Title: | Apoptotic contraction drives target cell release by cytotoxic T cells |
| Abstract: | Cytotoxic T lymphocytes (CTLs) fight intracellular pathogens and cancer by identifying and destroying infected or transformed target cells1. To kill, CTLs form a specialized cytotoxic immune synapse (IS) with a target of interest and then release toxic perforin and granzymes into the interface to elicit programmed cell death2–5. The IS then dissolves, enabling CTLs to search for additional prey and professional phagocytes to clear the corpse6. While the mechanisms governing IS assembly have been studied extensively, far less is known about target cell release. Here, we applied time-lapse imaging to explore the basis for IS dissolution and found that it occurred concomitantly with the cytoskeletal contraction of apoptotic targets. Genetic and pharmacological perturbation of this contraction response indicated that it was both necessary and sufficient for CTL dissociation. We also found that mechanical amplification of apoptotic contractility promoted faster CTL detachment and serial killing. Collectively, these results establish a biophysical basis for IS dissolution and highlight the importance of mechanosensory feedback in the regulation of cell–cell interactions. © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | human cell; genetics; apoptosis; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; perforin; target cell; feedback system; cell interaction; muscle contractility; cytoskeleton; dissociation; synapse; dissolution; granzymes; granzyme; synaptogenesis; time lapse imaging; article |
| Journal Title: | Nature Immunology |
| Volume: | 24 |
| Issue: | 9 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-09-01 |
| Start Page: | 1434 |
| End Page: | 1442 |
| Language: | English |
| DOI: | 10.1038/s41590-023-01572-4 |
| PUBMED: | 37500886 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is Morgan Huse -- Source: Scopus |
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