胸腺肽α1诱导MUC1特异性Th2型免疫应答

摘要

目的:采用黏蛋白与麦芽糖结合蛋白融合蛋白(MUC1-MBP)作为特异性抗原,研究胸腺肽α1 (Tα1)加强诱导 MUC1特异性免疫应答的类型,探讨其作为佐剂应用的可行性.方法:将C57BL/6小鼠随机分为生理盐水组(注射生理盐水)、MUC1-MBP+BCG 组(注射 MUC1-MBP+BCG)和 MUC1-MBP 和 Tα1组(注射 MUC1-MBP+Tα1),分别进行 T细胞免疫活性、MUC1特异性抗体效价及亚类、Tα1联合 MUC1-MBP抗肿瘤作用检测.第3次免疫后4~7d无菌取脾脏组织,测定脾指数;淋巴细胞增殖反应测定各组小鼠的刺激指数(SI);ELISA法测定小鼠脾细胞培养上清中干扰素γ(IFN-γ)、白细胞介素2(IL-2)、白细胞介素4 (IL-4)和白细胞介素10(IL-10)的水平及小鼠血清中 MUC1特异性抗体水平;第3次免疫后7 d,注射黑色素瘤细胞B16-MUC1,观察各组小鼠生存期.结果:与生理盐水组比较,MUC1-MBP+BCG组和 MUC1-MBP+Tα1组小鼠脾指数与 SI均升高(P0.05).与生理盐水组比较,MUC1-MBP+Tα1组小鼠脾细胞培养上清中 IL-4水平明显升高(P0.05).MUC1-MBP+Tα1免疫小鼠能够产生抗 MUC1特异性抗体且效价随浓度升高而升高.抗体亚型检测,与生理盐水组比较,MUC1-MBP+Tα1组 IgG1水平明显升高(P0.05);compared with normal saline group,the level of IL-4 in MUC1-MBP+Tα1 group was obviously increased(P0.05).The titer of MUC1 specific antibody was increased with the increase of concentration of Tα1.The antibody subtype detection results showed that compared with normal saline group,the level of IgG1 in MUC1-MBP+BCG group was significantly increased(P< 0.05 or P< 0.01),and the level of IgG2a had no obvious change.The tumor prevention experiment results showed that compared with normal saline group,the survival rates of the mice in MUC1-MBP+BCG group and MUC1-MBP+Tα1 group had no significant differences.Conclusion:MUC1-MBP combined with Tα1 prefers to Th2 immune responses in the mice.It indicates that Tα1 can be used as an adjuvanted preventive vaccines,but not suitable for therapeutic vaccines.