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Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation

Bettina Gebert, Wolfgang Fischer, Evelyn Weiss, Reinhard Hoffmann and Rainer Haas
Science
New Series, Vol. 301, No. 5636 (Aug. 22, 2003), pp. 1099-1102
Stable URL: http://www.jstor.org/stable/3834983
Page Count: 4
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Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation
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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.

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