小鼠红白血病细胞来源的树突状细胞对特异性CTL的体内外诱导作用

in vitro and in vivo Induction of Specific CTL by Dendritic Cells Derived from IL-12-Induced Erythroleukemia Cells

目的 探讨白细胞介素-12(IL-12)诱导小鼠红白血病细胞产生的树突状细胞,对白血病特异性CTL细胞的诱导作用,及体内免疫后对抗肿瘤免疫应答的诱导效果.方法:采用4/小时^(51)Cr释放法,检测CTL杀伤活性;观察小鼠红白血病细胞来源的树突状细胞体内免疫冶疗后对肿瘤的抑制作用,采用了HE染色和电镜等技术,分析肿瘤组织的病理学变化.结果:IL-12诱导FBL-3细胞产生的DC,在体外可诱导出FBL-3细胞特异性的CTL.采用IL-12诱导FBL-3细胞产生的DC免疫C57 BL/6小鼠.体内诱导出的CTL杀伤活性明显高于对照组.实验组小鼠能够有效的抵抗野生型FBL-3细胞的再攻击;肿瘤生长受到明显的抑制,组织学观察显示,肿瘤局部有较多炎性细胞浸润和细胞坏死;透射电镜可观察到典型的凋亡征象,结论:IL-12诱导小鼠FBL-3红白血病细胞产生的树突状细胞,在体内外可诱导出FBL-3细胞特异性的CTL,体内免疫后可增强抗肿瘤免疫应答,该结果为白血病的免疫治疗提供了新的途径.

Objective: To investigate the effects of DC derived from IL-12-induced erythroleukemia cells on the induction of CTL and protective antituinor immunity. Methods: The cytotoxicity of CTL was assessed by 4h 51 Cr-release assay. HE staining and eleclromicroscopy were used to observe the histological changes after immunized with erythroleukemia-derived DCs. Results: After incubation with naive T cells, the IL-12-induced FBL-3 cells could apparently induce the generation of CTL which exihibit the specific cytotoxicity against wild-type FBL-3 cells in vitro. We further assayed the cytotoxicity of CTL in vivo after immunized with erythroleukemia-derived DCs. CTL cytotoxicity of mice immunized with IL-12-in-duced FBL-3 cells was higher than that of mice immunized with IL-I2-uninduced FBL-3 cells. C57BL/6 mice immunized with IL-12-induced FBL-3 cells could resistant the subsequent rechallenge with the wild-type FBL-3 cells. The tumor growth was efficiently inhibited. Histological observation showed that more inflammatory cells infiltrated into the tumor tissue and necrosis of leukemia cells existed. By transmission electron microscopy, apoptositic phenomena were observed in the tumor of group immunized with IL-12-induced FBL-3 cells. However, these changes were not observed in the group immunized with IL-12-uninduced FBL-3 cells. Conclusion: These data indicate that erythroleukemia cells-derived DCs could induce specific CTL efficiently in vitro and in vivo, and may be used as new vaccine to activate antituinor immune responses.