Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1-deficient mice infected with Helicobacter pylori

To study the role of T cell responses in Helicobacter pylori gastritis, C57 BL/6 wild-type and interferon regulatory factor-1-deficient (IRF-1(-/-)) mi ce were infected with the mouse-adapted H. pylori Sydney strain. Mice lacki ng the transcription factor IRF-1 are defective in Th1 development and are therefore biased to mount a Th2-type response. After 4 months of infection, C57BL/6 mice developed severe gastritis and atrophy and mounted a Th1-type response towards H. pylori. The Th1 response was abrogated in IRF-1(-/-) m ice. This defective Th1 response was associated with the total lack of gast ritis and atrophy in IRF-1(-/-) mice despite severe colonization with H. py lori. In addition, IRF-1(-/-) mice did also not develop a Th2 reaction, sin ce they failed to generate H. pylori-specific antibodies and to produce IL- 4 in response to H. pylori antigens in vitro. Thus, the transcription facto r IRF-1 is necessary for the development of gastritis and atrophy in H. pyl ori-infected wild-type mice, suggesting a role of Th1 cells in the pathogen esis of H. pylori-associated diseases.