γ射线诱导癌细胞凋亡致敏树突状细胞后的免疫应答

Immune responses of dendritic cells after acquiring antigen from apoptotic hepatochlangioma cells caused by γ-ray

目的 观察树突状细胞 (DCs)从γ射线诱导的凋亡胆管癌细胞获取抗原后 ,抗肿瘤免疫应答及对胆管癌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胆管癌细胞凋亡 ,将DCs、T淋巴细胞和凋亡胆管癌细胞共培养 ,同时设计不同类型肿瘤细胞 (坏死胆管癌细胞及培养胆管癌细胞 )作对照 ,7d后 ,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 与凋亡胆管癌细胞共培养之DCs可以有效提呈胆管癌细胞抗原 ,有强烈的免疫应答 ,刺激的细胞毒T淋巴细胞 (CTLs)特异性地杀伤胆管癌细胞。结论 γ射线诱导癌细胞凋亡可以致敏rhGM CSF加rhIL 4从人外周血单核细胞诱导、扩增出的DCs并产生显著的杀伤胆管癌细胞的免疫反应 ,可望成为特异性免疫治疗肿瘤的一条新途径。

Objective To investigate the induction of cytotoxic T lymphocytes (CTLs) in antitumor responsiveness and therapeutic effects after dendritic cells (DCs) acquired antigen from apoptotic hepatochlangionma cells. Methods DCs from blood mononuclear cells that maintain the characteristics of immaturity-antigen-capturing and-processing capacity were established in vitro by using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4.Then,apoptosis in hepatochlangioma cells was induced with γ-radiation.The experimental groups included (1) coculture of DCs,and apoptotic cancer cells and T cells;(2)coculture of DCs necrotic cancer cells and T cells;(3)coculture of DCs-cultured cancer cell and T cells.These cells were cocutured for 7 days.DCs and T cell were enriched separately.Finally,antitumor response test was carried out. Results These cells had typical dendritic morphology,expressed high levels of CD1a,B7 and acquired antigen from apoptotic cells caused by γ-rays and induced an increased T cell-stimulatory capacity in MLR. Conclusions DCs obtained from blood mononuclear cells using GM-CSF and IL-4 and DCs can efficiently present antigen drived from apoptotic cells caused by γ-rays and induce T cells increasing obviously.It can probably become an effective approach of DC transduction with antigen.;