DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant.

DNA fragmentation: manifestation of target cell destruction mediated by cytotoxic T-cell lines, lymphotoxin-secreting helper T-cell clones, and cell-free lymphotoxin-containing supernatant.
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DNA 碎片:由细胞毒性 T 细胞系、分泌淋巴毒素的辅助 T 细胞克隆和含有淋巴毒素的无细胞上清液介导的靶细胞破坏的表现。

DOI:
10.1073/pnas.83.6.1881
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发表时间:
1986
影响因子:
11.1
通讯作者:
Ruddle,NH
Ruddle,NH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Schmid,DS;Tite,JP;Ruddle,NH

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Lyt-2+、三硝基苯基特异性的、分泌光敏素的细胞毒性T细胞系PC 155介导靶细胞DNA消化成离散大小的片段。这种现象在效应细胞相遇后30分钟内表现出来,如通过从用[3 H]脱氧胸苷预标记的靶细胞释放3 H计数所测量的,并且甚至在非常低的效应细胞与靶细胞比率(0.25:1)下也发生。Lyt-1+、卵清蛋白特异性的、分泌光敏素的T辅助细胞克隆5.9.24也能够在一段时间内介导靶细胞DNA的片段化,这与细胞毒性T淋巴细胞介导的命中基本上没有区别。无细胞的含光敏素的上清液也会导致DNA从靶上释放,尽管它们需要更长的时间过程,大约24小时。相反,通过抗体加补体或Triton X-100裂解细胞不会导致DNA释放,即使在延长的孵育期(24小时)后也是如此。导致DNA从细胞中释放的所有三种处理都会导致DNA片段化为离散大小的片段,这些片段是200个碱基对的倍数。因此,结果表明,细胞毒性T细胞,具有细胞溶解活性的α-光毒素分泌辅助克隆,和α-光毒素都通过类似的机制影响靶细胞破坏,并且观察到的时间过程的差异和α-光毒素介导的杀伤中靶细胞特异性的缺乏可能只是反映了毒素递送模式的差异。
A Lyt-2+, trinitrophenyl-specific, lymphotoxin-secreting, cytotoxic T-cell line, PCl 55, mediates the digestion of target cell DNA into discretely sized fragments. This phenomenon manifests itself within 30 min after effector cell encounter as measured by the release of 3H counts from target cells prelabeled with [3H]deoxythymidine and occurs even at very low effector to target cell ratios (0.25:1). A Lyt-1+, ovalbumin-specific, lymphotoxin-secreting T-helper cell clone, 5.9.24, is also able to mediate fragmentation of target cell DNA over a time course essentially indistinguishable from the cytotoxic T lymphocyte-mediated hit. Cell-free lymphotoxin-containing supernatants also cause release of DNA from targets, although they require a longer time course, on the order of 24 hr. In contrast, lysis of cells by antibody plus complement or Triton X-100 does not result in DNA release even after extended periods of incubation (24 hr). All three treatments that result in the release of DNA from cells cause fragmentation of that DNA into discretely sized pieces that are multiples of 200 base pairs. The results thus suggest that cytotoxic T cells, lymphotoxin-secreting helper clones with cytolytic activity, and lymphotoxin all effect target cell destruction by means of a similar mechanism and that observed differences in time course and the absence of target cell specificity in killing mediated by lymphotoxin may simply reflect differences in the mode of toxin delivery.