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小鼠细胞溶解淋巴细胞中一种新型细胞毒素的鉴定、分离与特性分析

Identification, isolation, and characterization of a novel cytotoxin in murine cytolytic lymphocytes.

作者信息

Liu C C, Steffen M, King F, Young J D

机构信息

Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.

出版信息

Cell. 1987 Nov 6;51(3):393-403. doi: 10.1016/0092-8674(87)90635-0.

DOI:10.1016/0092-8674(87)90635-0
PMID:3117375
Abstract

Murine cytotoxic T lymphocytes contain, in addition to the cytotoxic pore-forming protein perforin, another cytolytic factor localized in both cytoplasm and granules. Like perforin, this CTL cytotoxin lyses a variety of tumor cells; unlike perforin, it is stable in the presence of calcium, requires several hours to induce maximal lytic activity, and is antigenically related to the previously described tumor necrosis factor (TNF) and lymphotoxin (LT). However, it differs from TNF and LT in a number of biochemical and functional properties. TNF- and LT-specific cDNA probes did not hybridize with any CTL-specific message, indicating that the CTL cytotoxin is distinct from those two factors. It has an apparent Mr of 50 and 70 kd under reducing and nonreducing conditions, respectively, is secreted by secretagogue-stimulated CTLs, and causes DNA fragmentation in several targets, a phenomenon previously attributed to target cell damage by CTLs. These results suggest that killing by lymphocytes may encompass multiple mechanisms and polypeptides.

摘要

除细胞毒性成孔蛋白穿孔素外,小鼠细胞毒性T淋巴细胞还含有另一种定位于细胞质和颗粒中的溶细胞因子。与穿孔素一样,这种CTL细胞毒素可裂解多种肿瘤细胞;与穿孔素不同的是,它在有钙存在的情况下稳定,需要数小时才能诱导出最大溶细胞活性,并且在抗原性上与先前描述的肿瘤坏死因子(TNF)和淋巴毒素(LT)相关。然而,它在许多生化和功能特性上与TNF和LT不同。TNF和LT特异性cDNA探针未与任何CTL特异性信息杂交,表明CTL细胞毒素与这两种因子不同。在还原和非还原条件下,它的表观分子量分别为50和70kd,由促分泌剂刺激的CTL分泌,并在多个靶标中引起DNA片段化,这一现象以前被认为是CTL对靶细胞的损伤所致。这些结果表明,淋巴细胞杀伤可能涉及多种机制和多肽。

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