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目的:通过建立MCF-7荷瘤裸鼠模型,研究树突状细胞(DCs)不同亚群的凋亡,为设计新的免疫治疗方法和新的疫苗提供详尽信息。方法:建立MCF-7裸鼠模型,随机分为荷瘤组和对照组,肿块达5 mm后处死裸鼠,取骨髓单个核细胞进行DCs诱导、分化,流式细胞仪上检测表面分子标志CD86、CD83、MHC-Ⅱ及CD34,AnnexinⅤ检测CD11c及CD123了解DCs亚群的凋亡率。结果:骨髓起源单个核细胞培养至第9天出现典型DCs形态特征,荷瘤组和对照组细胞均高表达CD86、CD83及MHC-Ⅱ,而CD34表达两组均较低。荷瘤组CD11c+CD123-细胞为(52.01±1.43)%,对照组为(56.36±1.76)%;CD123+CD11c-细胞荷瘤组为(32.19±1.71)%,对照组为(28.95±1.39)%。荷瘤组mDC凋亡率为(23.64±2.43)%,较对照组(20.05±2.49)%高,P<0.05。荷瘤组小鼠pDC凋亡率为(11.53±2.92)%,较对照组(14.96±2.96)%低,P<0.05。结论:MCF-7乳腺癌小鼠体内DCs存在mDC和pDC两种亚型,mDC凋亡率增加,使诱导Th1免疫反应能力减低;而pDC凋亡率减少,诱导体内免疫耐受的发生,机体抗肿瘤免疫反应能力因而下降。
OBJECTIVE: To study the apoptosis of different subsets of dendritic cells (DCs) by establishing a model of MCF-7 tumor-bearing nude mice and provide detailed information for designing new immunotherapy methods and new vaccines. Methods: The model of MCF-7 nude mice was established and randomly divided into the tumor-bearing group and the control group. The nude mice were killed after the tumor mass reached 5 mm. The bone marrow mononuclear cells were induced and differentiated by DCs. The surface molecular markers CD86 , CD83, MHC-Ⅱ and CD34, AnnexinⅤ detection of CD11c and CD123 to understand the DCs subpopulation rate of apoptosis. Results: The morphological features of typical DCs appeared on day 9 after culture of bone marrow-derived mononuclear cells. CD86, CD83 and MHC-Ⅱ were highly expressed in both tumor-bearing and control cells, while CD34 expression was lower in both groups. The percentage of CD11c + CD123- cells in tumor-bearing group was (52.01 ± 1.43)% and that of control group was (56.36 ± 1.76)%, (32.19 ± 1.71)% in CD123 + CD11c- %. The apoptosis rate of mDC in tumor-bearing group was (23.64 ± 2.43)%, which was higher than that in control group (20.05 ± 2.49)%, P <0.05. The apoptosis rate of pDC in the tumor-bearing group was (11.53 ± 2.92)%, which was lower than that in the control group (14.96 ± 2.96)%, P <0.05. CONCLUSION: There are two subtypes of mDC and pDC in DCs of MCF-7 breast cancer mice, and the apoptosis rate of mDC is increased, so that the ability of inducing Th1 immune response is reduced. However, the apoptosis rate of pDC is decreased and the in vivo immune tolerance is induced. Anti-tumor immune response and thus decreased.