In vitro production of immunosuppressive factors by murine sarcoma virus-transformed mouse fibroblasts.

In vitro production of immunosuppressive factors by murine sarcoma virus-transformed mouse fibroblasts.
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鼠肉瘤病毒转化的小鼠成纤维细胞体外产生免疫抑制因子。

DOI:
10.1073/pnas.77.4.2205
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发表时间:
1980
影响因子:
11.1
通讯作者:
M. Hilfiker
M. Hilfiker
中科院分区:
综合性期刊1区
文献类型:
--
作者:
S. Mizel;J. Delarco;G. Todaro;W. Farrar;M. Hilfiker

文献摘要

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小鼠肉瘤病毒转化的小鼠成纤维细胞在体外产生强大的免疫抑制因子(ISF)。部分纯化的ISF可抑制刀豆蛋白A或植物血凝素+淋巴细胞激活因子(IL-1)诱导的胸腺细胞增殖、脂多糖诱导的脾细胞增殖、体外脾抗绵羊红细胞空斑形成细胞反应和同种异体抗原特异性细胞毒T细胞的产生。ISF对胸腺细胞增殖的影响不容易逆转,只需将胸腺细胞暴露在ISF中4小时即可抑制细胞增殖。虽然ISF与小鼠肉瘤病毒转化的细胞来源的肉瘤生长因子有几个生化特性(例如,醋酸的溶解性和对二硫苏糖醇的敏感性),但这两个因素可以通过Bio-Gel P-60凝胶过滤来解决。ISF活性有两个峰,表观分子量分别为12000和8000。这里描述的结果支持这样的假设,即至少从荷瘤宿主的血清中获得的部分ISF可能是由肿瘤细胞本身释放的。鉴于小鼠肉瘤病毒转化的成纤维细胞来源的ISF具有强大的体外活性,ISF样分子很有可能在涉及免疫系统的体内肿瘤排斥过程中发挥作用。
Murine sarcoma virus-transformed mouse fibroblasts produce potent immunosuppressive factors (ISF) in vitro. The partially purified ISF inhibited thymocyte proliferation induced by concanavalin A or phytohemagglutinin plus lymphocyte activating factor (Interleukin 1), lipopolysaccharide-induced spleen cell proliferation, the in vitro splenic anti-sheep erythrocyte plaque-forming cell response, and the generation of alloantigen-specific cytotoxic T cells. The effect of ISF on thymocyte proliferation was not readily reversible and required only a 4-hr exposure of the thymocytes to ISF to inhibit cell proliferation. Although ISF shares several biochemical properties with a murine sarcoma virus-transformed cell-derived sarcoma growth factor (e.g., acetic acid solubility and sensitivity to dithiothreitol), the two factors could be resolved by gel filtration on Bio-Gel P-60. Two peaks of ISF activity were found with apparent molecular weights of 12,000 and 8000. The results described here support the hypothesis that at least some of the ISF obtained from the serum of tumor-bearing hosts may be released by the tumor cells themselves. In view of the potent in vitro activity of the murine sarcoma virus-transformed fibroblast-derived ISF, it is quite possible that ISF-like molecules may play a role in subverting in vivo tumor rejection processes involving the immune system.