幽門螺旋桿菌之熱迫性蛋白60藉由引發調控性T細胞的產生而抑制週邊血液單核球之增生

Abstract

幽門螺旋桿菌是一種常見的腸胃道細菌，其特徵為可在腸道引發長期的慢性感染。目前有許多對於其毒力因子與免疫抑制上的相關研究，然而這些毒力因子並無法幫助每個亞種在體內生存。根據文獻探討，有一些物種的熱迫性蛋白在免疫上扮演著兩種截然不同的角色。例如來自Mycobacterium tuberculosis的熱迫性蛋白60便可引發調控性T細胞的增生來達到抑制免疫反應的目的。因此我們假設也許幽門螺旋桿菌的熱迫性蛋白60也許也有類似的功能。在我們的實驗中，我們利用週邊血液單核球以及CD3+ T細胞做為實驗對象來研究幽門螺旋桿菌熱迫性蛋白60是否對於調控性T細胞在CD4+ T細胞中的比例有所提昇。首先，我們先觀察該蛋白是否對細胞的增生有所影響。發現該蛋白對於週邊血液單核球的增生有嚴重的抑制。而對於週邊血液單核球的抑制乃是跟細胞生長的停滯有關。稍後我們想找出的這種抑制的現象是否跟調控性T細胞相關。在經過細胞表面抗原染色以及foxp3訊息RNA的表現程度顯示在經過幽門螺旋桿菌熱迫性蛋白60的刺激後，調控性T細胞在CD4+ T細胞中所佔的比例會有所上升。綜合上述所得到的結論，我們發現幽門螺旋桿菌之熱迫性蛋白60能夠促使調控性T細胞的比例上升，而這樣子的上升或許可以幫助幽門螺旋桿菌逃脫於免疫系統的攻擊。

H. pylori is a common gastrointestinal bacterium that causes chronic inflammation for lifelong. Many factors were investigated to see their functions on immune suppression. However, these factors may not be strong enough to help every stain escape from immune responses. According to the literature research, some members of heat shock proteins play a dual role in immune responses. For example, Mycobacterium tuberculosis hsp60 (Mt hsp60) protects the rat from arthritis by inducing Treg. Thus, we hypothesized that H. pylori heat shock protein 60 (Hp hsp60) might also induce Treg generation to suppress almost every population of immune cells. In our study, we used PBMC and CD3+ T cells as targets to investigate whether Hp hsp60 increases the percentage of Treg in CD4+ T cells. At first, we demonstrated the effect of Hp hsp60 on cell proliferation which is a character for immune cell activation. We found that Hp hsp60 has a strong suppressive ability for PBMC proliferation and a slight effect on Jurkat cells, which is a T lymphoma cell line. In addition, the proliferation inhibition was caused by cell arrest. The proliferation inhibition caused by Hp hsp60 might be due to the cell arrest. Furthermore, we intended to see whether this inhibition was associated with Treg. The CD4/CD25 double staining and foxp3 mRNA expression level showed that the Treg were increased after treated with Hp hsp60. Taken together, we found that Hp hsp60 could increase Treg cell generation and may help H. pylori escape from the immune system.