| Helicobacter pylori (H. pylori) infected over half of the adults of the world,especially in Asian-Pacific countries. Hoverver,only a small portion of patients displayed clinical symptoms such as peptic ulcer and gastric cancer. The difference between the infection and the outcomes was determined by both the bacterial factors and the host responses. Within the bacterial factors,the cag Pathogenicity Island (PAI) had been studied widely,while the immune response to the infection was the overwhelming host factor that affect the outcome of infection.Recent studieshave shown that cellular immunity,especially CD4+ T cells (helper T cell) play an important role in both the pathogenicity and prophylaxis of H. pylori infection. It might aggravate the gastric inflammation as well as intensify the damage of the gastric epithelium,wherevers,some phenotypes of this subset of T cell might protect the host from inflammation in naimal models. In this study,the selection of the subsets and phenotypes of T cells by H. pylori were investigated by both in vivo and in vitro studies. The effects of Thl/Th2 cytokines on the growth and the biological properties of gastric epithelial cells were determined too in vitro.In respect of the bacterial factors,cag A (cytotoxin associated gene A) protein used to be considered as a toxic marker of the bacterium. The related gene cluster,cag Pathogenicity Island (PAI) encoded several proteins with the similar biological activities. To define the relationship bwteen cagPAI and the pathogenicity of H. pylori,three pairs of H. pylori thathaboured cagPAI and their isogenic PAI knockout mutants were utilized. Their roles on the binding and apoptosis inducing activities as well as the immune protection were compared throughly. The results were as follows:1. The selection by H. pylori on the subsets of T cells.The surface and intracellular molecules of T cells were detected by flowcytometry. It was found that the infection with H. pylori was able to induce CD4+ T cells. The in vitro studies showed that the viable H. pylori,its sonicate peparation and the recombinant urease were all capable of selecting helper T cell response.2. The selection by H. pylori on the phenotypes of T cells.Both the in vivo and in vitro sudies showed that the viable H. pylori,its sonicate peparation and recombinant urease stimulated both Thl and Th2 response indiceted by the enhanced secrection of IFN-y and IL-4. Wherevers,the intensity of the upregulation of IFN-g secretion was greater than that of IL-4.3. The effect of Thl cytokine on the pathogenicity of H. pylori.Thl cytokine,IFN-y was able to increase the expression of MHC classll by gasric epithelial cells,thus,enhance the binding of H. pylori. Furthermore,IFN-y was capable of both inducing apoptosis of gastric epithelial cells alone or with H. pylori.4. The effect of Th2 cytokine on the pathogenicity of H. pylori.IL-10 receptor was detected on gastric epithelial cells,thus the biological property of this kind of cells might be regulated by IL-10. The in vitro studies showed that IL-10 inhibited the expression of MHC classll,down-regulatedthe binding of H. pylori as well asprotected the gastric epithelicl cells from apoptosis caused by IFN-y and H. pylori.5. The effect of cagPAI on the adherence of H. pylori to the gastric epithelial cells.No difference was found between cagPAI positive wildtype H. pylori and their PAI knockout mutants regarding to the binding activity to gastric epithelial cells.6. The effect of cagPAI on the apoptosis-inducing ability of H. pylori. There was no difference between the cagPAI positive wildtype H. pyloriand their PAI knockout mutants in respect of the apoptosis-inducing activity determined by both ELISA and agarose gel electrophoresis assays.7. The role of cagPAI on the immnune pprotection of H. pylori infection. The mice were immunized with the sonicate of H. pylori with PAIpositive or knockout strains plus adjuvant cholera toxin(CT),followed by the challenging with H,...
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