A coordinated cytotoxic effect of IFN-gamma and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori (H. pylori) infection is associated with chronic infiltration into the stomach by T cells and plasma cells producing IFN-gamma and antibodies of various specificities, respectively. It is unknown whether these lymphocyte-products may play coordinated roles in the gastric pathology of this infection. AIMS: To know how IFN-gamma may relate to anti-H. pylori antibodies in their roles in pathogenesis, we determined the isotype subclass of those antibodies as well as their cross-reactivity and cytotoxicity to gastric epithelium. METHODS AND
RESULTS: We infected BALB/c mice with H. pylori (SS1, Sydney Strain 1) and generated monoclonal antibodies, which were comprised of 240 independent clones secreting immunoglobulin and included 80 clones reactive to SS1. Ninety percent of the SS1-reactive clones had IgG2a isotype. Two clones, 2B10 and 1A9, were cross reactive to cell surface antigens in H. pylori and to antigens of 28 KDa and 42 KDa, respectively, which were present on the cell surface of and shared by both mouse and human gastric epithelial cells. The antigens recognized by these monoclonal antibodies localized a distinctive area in the gastric glands. In the presence of complement, 2B10 showed cytotoxicity to gastric epithelial cells. The effect was dose dependant and augmented by IFN-gamma. Finally, administration of 2B10 to mice with SS1 infection aggravated gastritis by increasing cellular infiltration.
CONCLUSION: IFN-gamma by gastric T cells may participate in pathogenesis of the H. pylori infected stomach by directing an isotype-switch of anti-H. pylori antibodies to complement-binding subclass and by augmenting cytotoxic activity of a certain autoantibody. This may explain a host-dependent diversity in gastric pathology of the patients with H. pylori infection.