Popis: |
OBJECTIVE: To study the protective immune response induced by Helicobacter pylori vaccine in mice. METHODS: Mice were orally immunized with cholera toxin (CT) plus H. pylori whole-cell sonicate antigen (group A), CT only (group B) or normal saline (group C), and challenged with H. pylori 4 weeks later. Mice from each group were killed at different time points before and after challenge. Gastric H. pylori colonization, serum anti-H. pylori IgG1, IgG2a and IgA antibodies, the mRNA expression of both Th1-type and Th2-type cytokines in the gastric mucosa and splenic tissue, and mucosal inflammation at different time points were compared among the groups. RESULTS: Colonization of H. pylori in group A decreased significantly compared with groups B and C at both 5 and 26 weeks after challenge. The serum concentrations of anti H. pylori IgG1, IgG2a and IgA in group A were significantly higher than those of groups B and C at all time points. The mRNA expressions of Th1-type cytokines in the gastric mucosa of groups A and B were higher than those of group C both before and 5 weeks after H. pylori challenge. At 26 weeks after challenge, Th1-type cytokines were increased in the gastric mucosa of group C, but decreased in the gastric mucosa of groups A and B, except for IL-12. Before challenge, Th2-type cytokines were expressed at a similar level in the gastric mucosa of both group A and group B; 5 weeks after challenge, IL-4 and IL-10 expressions were not detectable in either group and the expression of IL-6 in both groups was lower than that in group C; 26 weeks after challenge, the expression of both IL-4 and IL-10 was detected in group A, but only IL-10 in group B. The expression of IL-6 was similar in all groups. Both Th1- and Th2-type cytokines were expressed in the splenic tissue of all groups at different time points. Significant gastritis characterized by marked infiltration of mononuclear cells and neutrophils was found in group A at 5 weeks after challenge, but only mild inflammation was present in group B; 26 weeks after challenge, gastritis had increased in group C but decreased in the other two groups. CONCLUSIONS: The vaccine consisting of H. pylori whole-cell sonicate antigen and CT induces both Th1 and Th2 immune responses at an early stage. The Th1 response increases early after H. pylori challenge, which contributes to both protective immunity and postimmunization gastritis, whereas the Th2 response increases in the gastric mucosa late after challenge when both the Th1 response and postimmunization gastritis have abated. |