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Science 22 August 2003:
Vol. 301. no. 5636, pp. 1099 - 1102
DOI: 10.1126/science.1086871
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Reports

Helicobacter pylori Vacuolating Cytotoxin Inhibits T Lymphocyte Activation

Bettina Gebert, Wolfgang Fischer, Evelyn Weiss, Reinhard Hoffmann, Rainer Haas*

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.

Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, LMU München, Germany.

* To whom correspondence should be addressed. E-mail: haas{at}m3401.mpk.med.uni-muenchen.de

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