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H-2基因转染后自发性小鼠肺癌的致瘤性降低

Reduced tumorigenicity of a spontaneous mouse lung carcinoma following H-2 gene transfection.

作者信息

Bahler D W, Frelinger J G, Harwell L W, Lord E M

出版信息

Proc Natl Acad Sci U S A. 1987 Jul;84(13):4562-6. doi: 10.1073/pnas.84.13.4562.

DOI:10.1073/pnas.84.13.4562
PMID:3496596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC305130/
Abstract

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.

摘要

一种名为1号线的小鼠肺癌培养细胞表达的H-2 I类抗原水平极低,并且对同种反应性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基因转入1号线细胞。使用流式细胞术鉴定出显示H-2Dp表面抗原的克隆转染子。通过二维凝胶电泳,转染的H-2Dp抗原看起来正常,并且在体外也可以作为T细胞介导的裂解的良好靶标。仅当动物先前接受过辐照的Dp转染子注射时,在同基因小鼠中,Dp转染细胞与未转染或对照转染的1号线细胞之间才观察到致瘤性(定义为在免疫活性宿主中的肿瘤生长)存在明显差异。Dp抗原的表达并未明显影响免疫未致敏的同基因小鼠中1号线肿瘤的生长,也不一定会导致异基因小鼠中的肿瘤排斥。我们的体内结果表明,I类抗原表达的增加可以减少像1号线这样缺乏所有I类抗原的肿瘤的生长。我们的结果还表明,仅在一些表达缺陷的自发性肿瘤上增加I类抗原本身不足以实现肿瘤排斥。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c4/305130/9563bdebbd94/pnas00278-0219-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c4/305130/68299e02b86d/pnas00278-0219-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c4/305130/9563bdebbd94/pnas00278-0219-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c4/305130/68299e02b86d/pnas00278-0219-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04c4/305130/9563bdebbd94/pnas00278-0219-b.jpg

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