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

观察EG.7胸腺瘤细胞给药后肿瘤抗原特异性CD8 t细胞的时间变化，发现CTL活化维持较长时间，提示肿瘤复发的机制不取决于宿主侧，而取决于肿瘤侧。此外，在肿瘤免疫应答中效应CD8T细胞凋亡的细胞死亡中，通过Fas-FasL级联的信号转导很重要，而通过Bcl-2的信号转导不参与。这个结果是一个至今还没有得到澄清的事件。此外，为了分析Fas-FasL参与肿瘤抗原特异性CD8 t细胞凋亡的表达谱，我们构建了Fas基因靶向突变OT-I小鼠、FasL基因靶向突变OT-I小鼠和Bcl-2基因过表达OT-I小鼠。将Fas基因靶向突变的OT-I细胞或正常的OT-I细胞静脉输注到正常小鼠或Fas基因突变小鼠体内，构建嵌合体小鼠。

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.