抗原致敏外周血树突状细胞治疗脑胶质瘤的实验研究

Dendritic cells acquire antigen from apoptotic glioma cells and induce special CTLs

目的观察树突状细胞(DCs)从凋亡脑胶质瘤细胞获取抗原后,体外诱导抗肿瘤免疫应答及对胶质瘤细胞的特异性免疫杀伤效果。方法用粒-巨噬细胞集落刺激因子(GM-CSF)加白介素-4(IL-4)从人外周血分化、诱导DCs、γ-射线在体外诱导培养的人脑胶质瘤细胞凋亡,将DCs、T淋巴细胞和凋亡胶质瘤细胞共培养,同时设计不同类型肿瘤细胞(U937及培养胶质瘤细胞)作对照,分离、富集DCs、T淋巴细胞进行免疫应答及肿瘤细胞杀伤试验。结果与凋亡胶质瘤细胞共培养之DCs可以有效提呈胶质瘤细胞抗原,有强烈的免疫应答,刺激的细胞毒T淋巴细胞(CTLs)特异性杀伤胶质瘤细胞。结论用GM-CSF加IL-4从人外周血分化、诱导的DCs能从凋亡胶质瘤细胞有效提呈肿瘤抗原并诱导出显著的杀伤胶质瘤细胞的免疫反应,可望成为有效的肿瘤特异性免疫治疗新途径。

Objective To investigate the ability of dendritic cells（DCs）ac quiring antigen from apoptotic glioma cells and inducing CTLs activati on. Methods DCs were prepared from peripherad blood mononuclear induce d with gra-nulocyt e/macrophage colony-stimulating factor（GM-CSF） and interleukin-4. Apoptosis of glioma cells were induced withγ-radiation, We design these experi- ment groups including（ 1 ）coculture of DCs and apoptotic glioma cells and T cells, （2）coculture of DCs and U937 cells and T cells, （3）coculture of DCs and cultured glioma cell and T cells, （4）coculture of DCs and T cell. Results Only DCs cocultured with apoptofic cells can induce special CTLs, while the group o f U937 cells and culture ceils can not. Conclusion Human dendritic cells can efficiently present antigen derived from apoptotic cells and stimulate special CTLs. It will probably become effective especial anfitumor immunological therapeuty.