T细胞信号传递途径的改变与肿瘤免疫的关系

本室曾证明粒细胞.巨噬细胞集落刺激因子(GM-CSF)基因修饰的胎肝细胞脾内移植后,能选择性移入肝脏并在其中稳定表达外源基因,促进大剂量化疗后造血功能的恢复.本研究以大剂量化疗小鼠为实验模型,探讨了脾内移植CM-CSF基因修饰的胎肝细胞对化疗小鼠全身免疫功能恢复的影响.结果表明,脾内移植GM-CSF-FL组小鼠外周血CD4~ 细胞数及CD4~ /CD8~ 比值明显升高,脾细胞对ConA及LPS的增殖反应以及脾细胞NK活性显著增强,而骨髓细胞的NK活性及对丝裂原的增殖反应与对照组相比升高不明显,提示,脾内途径的GM-CSF基因疗法对大剂量化疗机体的免疫功能有显著促恢复作用,但对骨髓细胞免疫功能的恢复疗效不明显.

Acceleration of the Recovery of Chemotherapy-Induced Immune Suppression by the Intrasplenic Transplantation of GM-CSF Gene-Transfected Fetal Liver Cells

After murine fetal liver cells (FLC) were transfected with granulocyte-macrophage colony-stimulating factor (GM-CSF) gene by recombinant adenovirus and intrasplenically transplanted into allogeneic mice, the effects of GM-CSF gene-transfected FLC on the recovery of immune response inhibited by chemotherapy were observed. The number of CD4 cells and the ratio of CD4 /CDS cells from peripheral blood lymphocytes increased significantly. The cytotoxicity of the NK cells and the proliferation response of splenocytes to ConA, LPS elevated markedly, but the same results were not from bone marrow. These data demonstrated that intrasplenic transplantation of GM-CSF gene-transfected FLC could effectively accelerate the recovery of immune response after high-dose chemotherapy.