Application possibility of cancer immunotherapy by apoptotic regulation of effector CD8T cells

对EG.7胸腺瘤细胞接种后肿瘤抗原特异性CD8T细胞的时程变化观察表明，CTL活性维持时间较长，提示肿瘤复发的机制不是宿主侧的，而是肿瘤侧的。此外，在肿瘤免疫反应中效应CD8T细胞的凋亡细胞死亡中，通过Fas-FasL级联反应的信号转导显然是重要的，而通过Bcl-2的信号转导不参与。此外，为了分析肿瘤抗原特异性CD8 T细胞Fas-FasL的表达谱，构建了Fas基因靶向突变的OT-I小鼠、FasL基因靶向突变的OT-I小鼠和Bcl2基因过表达的OT-I小鼠。此外，将Fas基因靶向突变的OT-I细胞或正常的OT-I细胞静脉注射到正常小鼠或Fas基因突变的小鼠体内，构建了嵌合体小鼠。

Observation for time course changes of the tumor antigen specific CD8 T-cells after the administration of EG.7 thymoma cells revealed that the CTL activation was maintained for a long term, so it was suggested that the mechanism of the tumor relapse depend on not the host side but the tumor side. Moreover, in the apoptotic cell death of effector CD8T cells in the tumor immune response, it became clear that the signal transduction through Fas-FasL cascade was important, and it through Bcl-2 was not participating. This result is an event that has not been clarified up to now.In addition, in order to analyze the expression profile of Fas-FasL involving the apoptosis of the tumor antigen specific CD8 T-cells, Fas gene targeting mutated OT-I mouse, FasL gene targeting mutated OT-I mouse, and Bcl-2 gene overexpressed OT-I mouse were constructed. Moreover, Fas gene targeting mutated OT-I cell or a normal OT-I cell was transfused to the normal mouse or the Fas gene mutation mouse intravenously, and the chimera mouse wasconstructed.