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目的 研究幽门螺杆菌 (Helicobacterpylori,Hp)疫苗诱导小鼠保护性免疫应答的机制。方法 以霍乱毒素 (CT)加Hp全菌超声粉碎抗原免疫小鼠 ,并设CT组和生理盐水 (NS)组为对照。免疫 4周后以Hp攻击 ;在攻击前后不同时间点分批处死小鼠 ,比较免疫组和对照组胃黏膜Hp定植及各项免疫指标的变化。结果 (1)攻击后 5、2 6周后免疫组和CT组、NS组相比胃黏膜Hp定植量明显降低。 (2 )各时间点免疫组IgG1、IgG2a、IgA均高于NS组、CT组。 (3)攻击前和攻击后 5周免疫组和CT组胃黏膜Th1型细胞因子表达较NS组明显升高。攻击后 2 6周免疫组和CT组除白细胞介素 (IL) 12外 ,干扰素 (IFN) γ和IL 2表达均明显降低 ,而NS组Th1型细胞因子表达明显升高。 (4)Th2型细胞因子在攻击前免疫组和CT组胃黏膜均有轻度表达 ;攻击后 5周免疫组和CT组IL 4和IL 10均无表达 ,IL 6表达低于NS组 ;攻击后 2 6周免疫组IL 4和IL 10再次表达 ,CT组仅表达IL 10 ,IL 6表达各组无明显差异。 (5 )各细胞因子在所有组脾脏攻击前后各时间点表达无差异。 (6 )与NS组相比 ,攻击后5周免疫组鼠胃黏膜出现明显的炎症反应 ,CT组也有轻度炎症反应 ;攻击后 2 6周NS组炎症加重而免疫组则有所减轻。结论 (1)以CT为佐剂的Hp疫苗可诱导Th1和Th2混合型初始免疫?
Objective To study the mechanism of Helicobacter pylori (Hp) vaccine induced protective immunity in mice. Methods The mice were immunized with cholera toxin (CT) plus whole Hp pulsed antigen of H. pylori. CT and NS groups were used as controls. The mice were challenged with Hp 4 weeks after immunization. Mice were sacrificed in batches at different time points before and after challenge. The changes of Hp colonization and various immune indexes in the mucosa of the immunized and the control groups were compared. Results (1) The colonization rate of Hp in gastric mucosa of the immunized group, CT group and NS group was significantly decreased at 5 and 26 weeks after challenge. (2) The IgG1, IgG2a and IgA in the immunized groups at all time points were higher than those in the NS and CT groups. (3) The expression of Th1-type cytokines in gastric mucosa of the immunized group and CT group before and 5 weeks after challenge were significantly higher than those in NS group. At 26 weeks after challenge, the expression of IFN-γ and IL-2 were significantly decreased in both immunized and CT groups except for IL-12, while the expression of Th1-type cytokines in NS group was significantly increased. (4) Th2-type cytokines were mildly expressed in both the pre-challenge and CT-treated gastric mucosa. No expression of IL-4 and IL-10 was observed in the immunized and CT groups at 5 weeks post challenge IL-6 and IL-10 were re-expressed in the immunized group at 26 weeks after immunization, but no significant difference was observed in the expression of IL-10 and IL-6 in CT group. (5) There was no difference in the expression of various cytokines at all time points before and after spleen challenge in all groups. (6) Compared with the NS group, the gastric mucosa of the immunized group showed obvious inflammatory reaction 5 weeks after the challenge, and the CT group also had mild inflammatory reaction. At 26 weeks after the challenge, the inflammation of the NS group was aggravated and the immune group was relieved. Conclusions (1) CTV-adjuvanted Hp vaccine can induce mixed initial immunization of Th1 and Th2?