An inverse relation of the oncogenic potential of adenovirus-transformed cells and their sensitivity to killing by syngeneic natural killer cells.

An inverse relation of the oncogenic potential of adenovirus-transformed cells and their sensitivity to killing by syngeneic natural killer cells.
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腺病毒转化细胞的致癌潜力与其对同基因自然杀伤细胞杀伤的敏感性呈反比关系。

DOI:
10.1016/0042-6822(82)90290-2
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发表时间:
1982
期刊:
影响因子:
3.7
通讯作者:
Gallimore,PH
Gallimore,PH
中科院分区:
医学3区
文献类型:
--
作者:
RaskaJr,K;Gallimore,PH

文献摘要

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已经研究了五种腺病毒 (Ad) 转化细胞系对同基因自然杀伤 (NK) 和次级溶细胞 T 细胞杀伤的敏感性。转化的细胞系在体内具有不同的致癌潜力:A2T8细胞即使在免疫抑制的新生动物中也是非致瘤性的; T2C4细胞会在免疫抑制的新生大鼠中诱发肿瘤,但在未经治疗的新生大鼠中不会诱发肿瘤; 50A细胞对新生大鼠具有致瘤性; RFC1和RT2细胞在新生大鼠和断奶大鼠中均具有高度致癌性,并在成熟大鼠腹腔注射后诱发肿瘤。结果显示这些细胞对体外 NK 细胞毒性的敏感性与其体内致瘤潜力之间呈反比关系。竞争实验和效应细胞对单层靶细胞的吸附表明,所有五种测试的腺病毒转化细胞的抗原特异性均被同一 NK 细胞亚群识别。在平行实验中,没有检测到这些转化细胞系对同基因次级溶细胞 T 细胞杀伤的敏感性存在显着差异。 T 细胞杀伤分别对 Ad2 或 Ad12 转化细胞具有高度特异性。该系统中二次溶细胞 T 细胞的体外培养与 NK 活性的产生无关。这些结果表明,不同Ad转化细胞对自然细胞介导的细胞毒性杀死的敏感性,而不是其免疫原性,与它们的致癌潜力相关。
Sensitivity of five adenovirus (Ad) -transformed cell lines to killing by syngeneic natural killer (NK) and secondary cytolytic T cells has been studied. The transformed cell lines have different oncogenic potentialsin vivo: A2T8cells are nontumorigenic even in immunosuppressed newborn animals; T2C4cells induce tumors in immunosuppressed but not in untreated newborn rats; 50A cells are tumorigenic in newborn rats; RFC1and RT2cells are highly oncogenic in both newborn and in weanling rats and induce tumors after intraperitoneal injection to mature rats. The results show an inverse relation between the sensitivity of these cells to NK cytotoxicityin vitroand their tumorigenic potentialin vivo. Competition experiments and adsorptions of effector cells to monolayers of target cells indicate that antigenic specificities on all five tested adenovirus-transformed cells are recognized by the same subset of NK cells. In parallel experiments no significant differences were detected in sensitivity of these transformed cell lines to killing with syngeneic secondary cytolytic T cells. The T-cell killing was highly specific for Ad2- or Ad12-transformed cells, respectively.In vitroeducation of secondary cytolytic T cells in this system is not associated with generation of NK activity. These results suggest that sensitivity of different Ad-transformed cells to killing by natural cell-mediated cytotoxicity, rather than their immunogenicity, correlates with their oncogenic potential.