Cytotoxic T lymphocyte hybridomas that mediate specific tumor-cell lysis in vitro.

Cytotoxic T lymphocyte hybridomas that mediate specific tumor-cell lysis in vitro.
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介导体外特异性肿瘤细胞裂解的细胞毒性 T 淋巴细胞杂交瘤。

DOI:
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发表时间:
1981
影响因子:
11.1
通讯作者:
Z. Eshhar
Z. Eshhar
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Y. Kaufmann;G. Berke;Z. Eshhar

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通过聚乙二醇诱导的细胞毒性T淋巴细胞(CTL)和BW 5147淋巴瘤细胞的融合产生细胞毒性杂交瘤。用于融合的CTL群体从用C57 BL/6(H-2b)的白血病EL 4致敏的BALB/c(H-2d)小鼠获得,并在体内或体外再刺激。为了避免融合过程中CTL介导的BW 5147细胞的非特异性裂解,在融合前用胰蛋白酶瞬时灭活CTL。获得、克隆和亚克隆四个具有细胞溶解活性的杂交瘤。杂交克隆溶解所有测试的H-2b白血病靶细胞,但不溶解脂多糖或刀豆素A刺激的C57 BL/6成淋巴细胞或非H2 b靶肿瘤细胞。杂交瘤介导的体外杀伤靶细胞的机制似乎与亲本CTL的机制相似,尽管已经观察到一些差异。杂交瘤似乎既不具有自然杀伤作用,也不具有抗体依赖性细胞溶解活性。在不添加已知的外部刺激(即,不依赖于细胞生长因子和抗原)对H-2b肿瘤细胞显示特异性溶解活性。这种自主杂交瘤将为研究CTL介导的裂解机制和CTL受体的性质提供工具。
Cytotoxic hybridomas were generated by polyethylene glycol-induced fusion of cytotoxic T lymphocytes (CTL) and BW5147 lymphoma cells. The CTL populations used for fusion were obtained from BALB/c (H-2d) mice primed with leukemia EL4 of C57BL/6 (H-2b) and restimulated either in vivo or in vitro. To circumvent possible CTL-mediated nonspecific lysis of BW5147 cells during fusion, the CTL were transiently inactivated by trypsin prior to fusion. Four cytolytically active hybridomas were obtained, cloned, and subcloned. Hybrid clones lysed all H-2b leukemic target cells tested but not lipopolysaccharide- or concavanalin A-stimulated C57BL/6 lymphoblasts or non-H2b target tumor cells. The mechanism of hybridoma-mediated killing of target cells in vitro appears to be similar to that of parental CTL, although some differences have been observed. The hybridomas appear to possess neither natural killing nor antibody-dependent cytolytic activity. Clones of hybrids propagated in culture for over 6 months without the addition of known external stimulus (i.e., independent of cell growth factor and antigen) exhibit specific lytic activity against H-2b tumor cells. Such autonomous hybridomas will provide a tool for studying the mechanism of CTL-mediated lysis and the nature of the CTL receptors.