MHC Ⅱ类基因修饰的小鼠黑色素瘤细胞对肿瘤特异性CTL诱导的实验研究  

Experimental studies on tumor specific CTL induction with MHC class Ⅱ gene modified murine melanoma

作　　者：隋拥君[1] 唐佩弦[1] 侯春梅[1] 隋礼丽[2] 毛宁[1] 

机构地区：[1]北京基础医学研究所,北京100850 [2]南方医院传染病科,广州510515

出　　处：《中国实验血液学杂志》1998年第2期124-128,共5页Journal of Experimental Hematology

摘　　要：大多数的肿瘤细胞只表达MHCⅠ类抗原,不表达Ⅱ类抗原,而Ⅱ类抗原主要与T辅助细胞作用,激活T辅助细胞,为细胞毒性T淋巴细胞(CTL)的活化提供必需的辅助信息。如果肿瘤细胞是MHCⅡ类阳性的,就可以直接作为抗原提呈细胞来刺激T辅助细胞的增殖,进而产生有效的免疫反应,因此向肿瘤细胞内转移MHCⅡ类基因是目前正在尝试的一种新的基因治疗方法。为了探讨MHCⅡ类基因修饰的肿瘤细胞其免疫原性的变化,我们利用已经获得的表达MHCⅡ类基因的B16-DR细胞,进行CTL诱导的实验研究。结果表明,经MHCⅡ类基因修饰的B16-DR细胞可以在体内和体外诱导产生针对原始B16细胞的CTL反应,而未经修饰的B16细胞却无此作用。此CTL反应可用抗MHCⅡ的单克隆抗体封闭,并且封闭的程度随着加入的抗体量的增加而增加,说明此CTL反应的诱导与所转入的MHCⅡ类基因密切相关。抗CD4/CD8的单克隆抗体可以阻断CTL的诱导,表明T辅助细胞和杀伤性T细胞也参与了这一CTL诱导过程。总之,我们的实验结果提示所转入的MHCⅡ类基因以及CD4和CD8T细胞在CTL诱导反应中具有重要作用。Most tumor celis express major histocompatibility complex (MHC) class Ⅰ but not class Ⅱ molecules, which mainly interacts with and activates T helper cells and provides help Information for the CTL activation. Immune responses may be more efficient if tumor cells were class Ⅱpositive, and thereby able to directly func-tion as antigen presenting cell to stimulate T helper cell prolif eration. Recently, a unique gene therapy approach has been developed to introduce genes encoding MHC class Ⅱ antigens to tumor cells. In order to investigate the immunogenicity of MHC class Ⅱ modified melanoma cell line, B16-DR celis which expressed MHC class Ⅱ genes were used to study the ability of tumor-specific CTL induction. The resuhs showed that MHC class Ⅱ modified B16-DR celis could induce wild type tumor-specific CTL both in vivo and in vitro, while the unmodi-lied B16 celis had no such effect. The fact that anti-MHC class Ⅱ McAb could block CTL induction and more antibody was added, more completely CTL induction reaction was blocked suggests the close relationship be-tween MHC class Ⅱ gene transfer and CTL induction. CD4/CD8 McAb could also abrogate CTL induction, which showed that both CD4 and CD8 T celis took part in CTL induction. In summary, our experimental resuhs demonstrate the important role of transfected MHC class Ⅱ and CD4/CD8 T cells in the CTL induction.

关 键 词：MHC Ⅱ类基因 黑色素瘤 细胞毒性T淋巴细胞 B16-DR细胞 

分 类 号：R739.5[医药卫生—肿瘤]