Clearance of Helicobacter pylori infection through immunization:: the site of T cell activation contributes to vaccine efficacy

Helicobacter pylori vaccine development has progressed rapidly in animal models. Both H. pylori-associated pathogenesis and protective immunity are CD4(+) T cell dependent, with no discernable phenotypic difference to distinguish pathogenic T cells from protective T cells. Functionally however, protective T cells promote enhanced inflammation upon H. pylori challenge. Additionally, only mouse models such as phagocyte oxidase- or IL-10-deficient mice that respond to H. pylori infection with intense gastritis are capable of demonstrating spontaneous eradication of the bacteria. These data, combined with recent descriptions of down-regulatory T cells in infected humans and mice, support an emerging model of H. pylori pathogenesis in which H. pylori induces inflammation that is limited by regulatory T cells in the stomach. Immunization therefore may succeed by activating T cells in peripheral lymph nodes that are capable of promoting qualitatively or quantitatively different inflammation when recruited to the stomach. Evidence in support of this model will be discussed. (C) 2003 Elsevier Ltd. All rights reserved.