Gebert Bettina, Fischer Wolfgang, Weiss Evelyn, Hoffmann Reinhard, Haas Rainer
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, LMU München, Germany.
Science. 2003 Aug 22;301(5636):1099-102. doi: 10.1126/science.1086871.
Helicobacter pylori (Hp) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G1/S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca2+-calmodulin-dependent phosphatase calcineurin. Nuclear translocation of nuclear factor of activated T cells (NFAT), a transcription factor acting as a global regulator of immune response genes, was abrogated, resulting in down-regulation of IL-2 transcription. VacA partially mimicked the activity of the immunosuppressive drug FK506 by possibly inducing a local immune suppression, explaining the extraordinary chronicity of Hp infections.
幽门螺杆菌（Hp）空泡毒素VacA可诱导上皮细胞发生细胞空泡化。我们发现，VacA可通过诱导G1/S期细胞周期阻滞有效阻断T细胞增殖。它在Ca2+ - 钙调蛋白依赖性磷酸酶钙调神经磷酸酶水平干扰T细胞受体/白细胞介素-2（IL-2）信号通路。活化T细胞核因子（NFAT）作为免疫反应基因的全局调节因子，其核转位被消除，导致IL-2转录下调。VacA可能通过诱导局部免疫抑制部分模拟免疫抑制药物FK506的活性，这解释了Hp感染的异常慢性化。
