Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities.
Studies on cytotoxicity generated in human mixed lymphocyte cultures. I. Time course and target spectrum of several distinct concomitant cytotoxic activities.
复制标题
对人类混合淋巴细胞培养物中产生的细胞毒性的研究。
DOI：
10.4049/jimmunol.120.4.1415
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发表时间：
1978
影响因子：
4.4
通讯作者：
Sidney H. Golub
中科院分区：
文献类型：
--
作者：
Janet K. Seeley;Sidney H. Golub
人类混合淋巴细胞培养(MLC)被观察到不仅对同种异体特异性靶细胞产生细胞毒作用，而且对同种异体对照靶细胞产生细胞毒作用。这项工作调查了对MLC激活的效应器敏感的靶细胞的类型，并分析了这些活动产生的时间进程。正常人外周血淋巴细胞(PBL)在MLC中被正常同种异体丝裂霉素C处理的PBL致敏，随后在51Cr释放细胞介导的淋巴溶解(CML)试验中检测对不同靶点的细胞毒作用。根据对效应物敏感的靶细胞的类型，可以清楚地区分两种类型的细胞毒作用：a)异体细胞毒作用针对相关的同种异体ConA母细胞(异体母细胞)，而不是针对本土对照ConA母细胞(自身母细胞)。B)相反，“异常”细胞毒性，最初被定义为对自身淋巴母细胞系(AUTO-LCL)靶标的同种异体激活的细胞毒性，被证明对所测试的所有培养的细胞系靶标具有广泛的细胞毒活性。通过对这些活性在培养中的发育时间的研究，进一步区分了异位细胞毒性和“异常”反应性。异常活性高峰期总是提前1~2天，且比异位细胞毒性峰值下降得更快。在致敏细胞和对异常细胞毒性敏感的靶点之间寻找共同的抗原决定簇的实验表明，没有明显的抗原关系。
Human mixed lymphocyte cultures (MLC) have been observed to generate cytotoxicity not only against allospecific targets but also against autochthonous control target cells. This work investigates the types of target cells susceptible to the MLC-activated effectors and also analyzes the time course of the generation of these activities. Normal human peripheral blood lymphocytes (PBL) were sensitized to normal allogeneic mitomycin C-treated PBL in MLC and subsequently were tested for cytotoxicity against various targets in a 51Cr-release cell-mediated lympholysis (CML) assay. Two types of cytotoxic activities were clearly distinguishable by the types of target cells susceptible to the effectors: a) The allocytotoxicity was directed at the relevant allogeneic Con A blasts (alloblasts), but not to the autochthonous control Con A blast (autoblast) targets. b) In contrast, the “anomalous” cytotoxicity, which was originally defined as alloactivated cytotoxicity against the autochthonous lymphoblastoid cell line (auto-LCL) target, was shown to have a broad range of cytotoxic activity against all cultured cell line targets tested. The allocytotoxicity was further distinguished from the “anomalous” reactivity by studies on the time of development in culture of these activities. The peak anomalous activity always occurred 1 or 2 days earlier and declined more rapidly than the peak allocytotoxicity. Experiments to find common antigenic determinants between the sensitizing cells and targets susceptible to anomalous cytotoxicity revealed no obvious antigenic relationships.