细胞毒性T细胞
穿孔素
细胞生物学
颗粒酶
CTL公司*
细胞凋亡
细胞内
收缩(语法)
细胞
化学
免疫系统
免疫突触
生物
T细胞
免疫学
生物化学
T细胞受体
内分泌学
体外
作者
Elisa E. Sanchez,María Tello-Lafoz,Aixuan J. Guo,Miguel de Jesús,Yassmin A. Elbanna,Benjamin Y. Winer,Sadna Budhu,Eric Chun Yong Chan,Eric Rosiek,Taisuke Kondo,Justyn DuSold,Naomi Taylor,Grégoire Altan‐Bonnet,Michael F. Olson,Morgan Huse
标识
DOI:10.1038/s41590-023-01572-4
摘要
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.
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