幽门螺杆菌疫苗免疫小鼠的Th免疫应答及作用  

Th type immune response induced by Helicobacter pylori vaccine in mice

作　　者：陈洁[1] 陈旻湖[1] 李国庆[1] 焦志勇[1] 梁伟强[2] 胡品津[1] 沈祖尧[2] 

机构地区：[1]中山大学附属第一医院消化内科,广州510080 [2]香港中文大学威尔斯亲王医院内科及药物治疗系

出　　处：《中华消化杂志》2003年第12期739-743,共5页Chinese Journal of Digestion

基　　金：卫生部临床学科重点项目 (970 40 2 2 6);广东省科技计划重点攻关项目(99M 0 480 2G);广东省自然科学基金课题 (990 0 77)

摘　　要：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 protective immune response induced by Helicobacter pylori (H. pylori) vaccine in mice. Methods Mice were orally immunized with cholera toxin(CT) plus H. pylori whole cell sonicate antigen, CT or normal saline(NS) respectively. Four weeks after immunization mice were challenged with H. pylori. Mice were sacrificed at different time points before and after challenge. Gastric H. pylori colonization, serum anti H. pylori IgG1, IgG2a and IgA antibodies, mRNA expressions of Th1 type cytokines including interferon(IFN) γ, interleukin(IL) 2, IL 12 and Th2 type cytokines including IL 4, IL 6, IL 10 in gastric mucosa and spleen, and gastric inflammation at different time points were all compared in different groups. Results (1) H. pylori colonization in CT plus sonicate antigen group was decreased significantly compared with CT group and NS group both 5 and 26 weeks after challenge. (2)The serum levels of anti H. pylori IgG1, IgG2a and IgA of CT plus sonicate antigen group were significantly higher than those of CT group and NS group at all time points. (3)The mRNA expression levels of Th1 type cytokines in the gastric mucosa of CT plus sonicate antigen group and CT group were higher than that of NS group both before and 5 weeks after H. pylori challenge. 26 weeks after the challenge, Th1 type cytokines in the gastric mucosa of NS group were increased, but those in the gastric mucosa of CT plus sonicate antigen group and CT group were decreased except for IL 12. (4)Before the challenge, Th2 type cytokines were expressed similarly in the gastric mucosae of both CT plus sonicate antigen group and CT group. 5 weeks after the challenge, IL 4 and IL 10 expressions were not detected in CT plus sonicate antigen group and CT group and the expression of IL 6 was lower than that of NS group. 26 weeks after the challenge, both IL 4 and IL 10 expressed again in CT plus sonicate antigen group, but only IL 10 expressed again in CT group. The expressions of

关 键 词：幽门螺杆菌 疫苗 小鼠 免疫应答 胃炎 Thl反应 TH2反应 

分 类 号：R392[医药卫生—免疫学]