摘要
目的观察在肿瘤生长过程中DCs的功能是否存在变化,并探讨其意义。方法建立小鼠乳腺癌动物模型,用FACS分析荷瘤早、晚期时间点肿瘤浸润淋巴细胞中DCs的比例及其MHC-Ⅱ类分子和协同刺激分子CD80、CD86的表达;用ELISA法检测DCs的细胞因子IL-4、IL-10、IFN-γ和TNF-α的分泌情况;观察DCs对CD4+T细胞增殖及对CD8+T细胞杀伤功能的影响。结果与荷瘤早期相比,荷瘤晚期肿瘤浸润淋巴细胞中DCs的比例从11.76±2.3%增加到17.45±3.2%(p<0.05);晚期DCs下调表达MHC分子及协同刺激分子CD86,而上调表达IL-4、IL-10;晚期DCs刺激CD4+T细胞增值的能力明显减弱,并且对CD8+T细胞的杀伤能力的刺激作用也显著降低。结论随着荷瘤时间的延长,DCs的成熟度及其对T淋巴细胞的免疫刺激作用逐渐降低,这可能与肿瘤的免疫逃逸密切相关。
Objective To elucidate the functional changes of dendritic cells during the tumor progress and its significance in tumor immunity. Methods An experimental animal model of mouse mammary carcinoma was established. The percentage of CD11c^+ DCs in tumor infiltration lymphocytes in the early and late stage of tumor progress was detected by FACS. Then the expression of MHC-class Ⅱ molecule and co-stimulatory molecules CD80 and CD86 on CD11c^+ DCs also were analyzed. Furthermore, the cytokine secretion including IL-4, IL-10, IFN-γ and TNF-α from CD11c^+ DCs was determined by ELISA. Finally, the effects of CD11c^+ DCs on the proliferation of CD4^+T cells, as well as the cytotoxicity of CD8^+T cells were determined. Results The percentage of CD11c^+ DCs in the late stage of tumor progress was significantly higher than that in the early stage (p〈0.05), which were 17.45±3.2% and 11.76±2.3% respectively.Furthermore, the expression of MHC-class Ⅱ molecule and the co-stimulatory molecules on CD11c^+ DCs decreased significantly in the late stage compared with that in the early stage. On the contrary, IL-4 and IL-10 secretion of CD11c^+ DCs increased dramatically in the late stage of tumor progress. Finally, the stimulatory effects of CD11c^+DCs on the proliferation of CD4^+ T cells, as well as the cytotoxicity of CD8^+ T cells, decreased obviously in the late stage of tumor progress compared with that in the early stage. Conclusions The maturation status and the stimulatory effects of CD11c^+ DCs gradually decreased during the tumor progression, which might be closely related to the immune escape of tumor.
出处
《遵义医学院学报》
2008年第2期116-119,共4页
Journal of Zunyi Medical University