Reduced tumorigenicity of a spontaneous mouse lung carcinoma following H-2 gene transfection.
Reduced tumorigenicity of a spontaneous mouse lung carcinoma following H-2 gene transfection.
复制标题
H-2 基因转染后自发性小鼠肺癌的致瘤性降低。
DOI：
10.1073/pnas.84.13.4562
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发表时间：
1987
影响因子：
11.1
通讯作者：
Lord,EM
中科院分区：
文献类型：
--
作者：
Bahler,DW;Frelinger,JG;Harwell,LW;Lord,EM
被称为细胞系1的鼠肺癌的培养细胞表达非常低水平的H-2 I类抗原，并且对同种异体反应性T细胞介导的裂解具有抗性。为了研究I类抗原的表达如何影响这种自发性肿瘤的体内生长，将H-2Dp基因转移到1系细胞中。使用流式细胞术鉴定展示H-2Dp表面抗原的克隆转染子。转染的H-2Dp抗原通过二维凝胶电泳显示正常，并且也可以作为体外T细胞介导的裂解的良好靶点。仅当动物先前接受过辐照Dp转染子注射时，在同基因小鼠中Dp转染细胞和未转染或对照转染的1系细胞之间观察到致瘤性（定义为免疫活性宿主中的肿瘤生长）的显著差异。Dp抗原的表达并没有明显影响免疫幼稚同基因小鼠中1号线肿瘤的生长，也不一定会引起异基因小鼠的排斥反应。我们的体内结果表明，I类抗原的表达增加可以减少肿瘤的生长，如缺乏所有I类抗原的1号系。我们的研究结果还表明，增加I类抗原单独对一些自发性肿瘤的表达缺陷本身将不足以肿瘤排斥。
Cultured cells of the murine lung carcinoma called line 1 express very low levels of H-2 class I antigens and are resistant to lysis mediated by alloreactive T cells. In order to investigate how the expression of class I antigens affects the in vivo growth of this spontaneous tumor, H-2Dp genes were transferred into line 1 cells. Cloned transfectants that displayed H-2Dp surface antigens were identified using flow cytometry. The transfected H-2Dp antigens appeared normal by two-dimensional gel electrophoresis and could also function as excellent targets for T-cell-mediated lysis in vitro. Marked differences in tumorigenicity (defined as tumor growth in immunologically competent hosts) were observed between the Dp transfected cells and untransfected or control transfected line 1 cells in syngeneic mice only if the animals had previously received injections of irradiated Dp transfectants. Expression of Dp antigens did not appreciably affect the growth of line 1 tumors in immunologically naive syngeneic mice or necessarily cause rejection in allogeneic mice. Our in vivo results show that increased expression of class I antigens can reduce the growth of tumors like line 1 that lack all class I antigens. Our results also suggest that increasing class I antigens alone on some spontaneous tumors deficient in expression will not by itself be sufficient for tumor rejection.