Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation

Abstract

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 G 1 /S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca 2 + -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.