Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation¹

Speaker: 伍展弘                      Time: 2003/11/12  3:00-4:00 pm

Commentator: 許博翔 醫師                           Place: Room 601

Helicobacter pylori virulence factor, VacA, is a secreted 95 kD protein, which has been observed for its vaculation and the function of causing apoptosis². To establish a chronic infection, H. pylori possibly evades host responses through the inhibition of antigen specific T cell proliferation³. In this paper, the authors had a great interest on investigating H. pylori-T cell interactions. They first focused on a strong reduction of Jurkat T cell proliferation by using H. pylori-infected T cells. Then they examined the IL-2 secretion, which was an index of efficient activation and proliferation of T cells. As a result, they found that secreted H. pylori VacA plays a pivotal role in blocking T cell activation and proliferation at the stage of IL-2 signaling. To demonstrate that VacA efficiently blocked IL-2 production at the transcription level, they tested several transcription factors that had been identified as essential for activation of the IL-2 gene promoter. However, the IL-2 gene was strongly silenced when NFAT was blocked by VacA. Moreover, they improved that the VacA did not interact with NFAT directly but blocked the signaling cascade at the level of the phosphatase calcineurin, or further upstream. Finally, the authors used microarray analysis to search possible genes that were regulated by VacA and FK506, an important immunosuppressive drug that inhibit calcineurin activity. They found VacA partially mimicked the activity of drug FK506. Based on the above results, the authors suggested that VacA inhibits T lymphocyte by inducing a local immune suppression and cell cycle arrest.

References:

1.      Bettina Gebert et al. Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation. Science 301: 1099-1102 (2003)

2.      Jean-Marc Reyrat et al. Towards deciphering the Helicobacter pylori cytotoxin. Mol Microbio 34: 197-204 (1999)

3.      Sebastian Suerb et al. Helicobacter pylori infection. N Engl J Med 347: 1175-1186 (2002)