Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.
Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.
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细胞毒性 T 淋巴细胞触发的靶细胞死亡：靶细胞突变体区分被动孔形成和主动细胞自杀机制。
DOI：
10.1128/mcb.14.1.427-436.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Hebshi,LD
中科院分区：
文献类型：
--
作者：
Ucker,DS;Wilson,JD;Hebshi,LD
靶细胞在细胞毒性T淋巴细胞（CTL）介导的自身死亡中的作用一直存在争议。CTL的成孔颗粒组分直接诱导靶细胞死亡的能力已被认为是该靶的基本上被动的作用。这种CTL介导的杀伤的观点将向CTL提供抗原刺激的单一作用归因于靶标;该信号导致载体脱粒和孔形成元件分泌到靶标上。另一方面，根据许多标准，由CTL触发的靶细胞死亡似乎与由膜损伤和渗透溶解引起的死亡根本不同。CTL触发的靶细胞死亡涉及反映生理性细胞死亡过程的靶细胞的原发性内部病变。有序的核解体，包括核纤层蛋白磷酸化和溶解，染色质凝聚，和基因组消化，是最早的事件，在质膜完整性的损失。我们已经直接测试了靶细胞在其自身死亡中的参与，通过检查我们是否可以分离出保留被CTL识别并向CTL提供抗原刺激的能力而失去通过死亡应答的能力的靶细胞突变体。在这里，我们描述了一个这样的突变体，BW 87。我们已经使用这种CTL抗性突变体来分析在各种条件下CTL触发的靶细胞死亡的机制。对CTL的细胞死亡应答所必需的可变靶细胞元件的鉴定提供了靶细胞死亡反映类似于其他生理细胞死亡的主动细胞自杀过程的遗传证据。
The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes to the target the single role of providing an antigenic stimulus to the CTL; this signal results in the vectoral degranulation and secretion of pore-forming elements onto the target. On the other hand, by a number of criteria, target cell death triggered by CTL appears fundamentally different from death resulting from membrane damage and osmotic lysis. CTL-triggered target cell death involves primary internal lesions of the target cell that reflect a physiological cell death process. Orderly nuclear disintegration, including lamin phosphorylation and solubilization, chromatin condensation, and genome digestion, are among the earliest events, preceding the loss of plasma membrane integrity. We have tested directly the involvement of the target cell in its own death by examining whether we could isolate mutants of target cells that have retained the ability to be recognized by and provide an antigenic stimulus to CTL while having lost the capacity to respond by dying. Here, we describe one such mutant, BW87. We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered target cell death under a variety of conditions. The identification of a mutable target cell element essential for the cell death response to CTL provides genetic evidence that target cell death reflects an active cell suicide process similar to other physiological cell deaths.