Protective and pathogenic functions of T-cells are inseparable during the Helicobacter-host interaction.
Chronic infection with the bacterial pathogen Helicobacter pylori is closely linked to the development of gastric cancer. Experimental infection of the laboratory mouse strain C57Bl6 mimics the initiation and progression of the disease in humans. Using this model, we have identified a dual role for CD4+ IFN-gamma-secreting T-cells in the control of Helicobacter infection as well as in the induction of preneoplastic gastric pathology. High gastric expression of IFN-gamma was positively correlated with a low Helicobacter burden, and was essential for vaccine-induced protection; on the other hand, elevated levels of the cytokine also, either directly or indirectly, triggered the transformation of the normal gastric mucosa to atrophic, hyperplastic and metaplastic lesions. Based on similar patterns of gene expression changes induced by IFN-gamma in vivo and in cultured gastric epithelial cells, we hypothesize that IFN-gamma may act directly on epithelial cells to stimulate their hyperproliferation, and thus to predispose them to elevated mutation rates and an increased risk of malignant transformation.
Institute of Molecular Cancer Research, University of Zurich, Zurich 8057, Switzerland. mueller@imcr.uzh.ch
Anne
A
Mueller
Ayca
A
Sayi
Iris
I
Hitzler
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013274:Stomach Neoplasms / Q000209:etiology / Q000276:immunology / Q000382:microbiology
D007371:Interferon-gamma