title: Helicobacter-specific cell-mediated immune responses display a predominant Th1 phenotype and promote a delayed-type hypersensitivity response in the stomachs of mice.
abstract: Studies regarding the nature of cell-mediated immunity in Helicobacter pylori infection and its role in pathogenesis have yielded controversial results. To address this issue in a controlled manner, we have employed the well-characterized Helicobacter felis-mouse model. Immunized/challenged and nonimmunized/infected mice were evaluated for cellular proliferation, gastric inflammation, and cytokine and Ab production at various times after infection. We observed two types of cell-mediated immune responses depending on the nature of the Ag preparation. The first response is a Helicobacter-independent response, present in all experimental groups, which is directed toward Ags such as urease and heat shock proteins. The second is a Helicobacter-dependent cellular response restricted to mice previously exposed to Helicobacter Ags either by immunization or infection. This response was not seen in noninfected controls. The Helicobacter-dependent cellular response had a Th1 phenotype, as either infected or immunized/challenged mice demonstrated local and systemic production of IFN-gamma and undetectable levels of IL-4 or IL-5. Cellular proliferation correlated with the severity of gastric inflammation in both immunized/challenged (protected) and nonimmunized/infected mice. Finally, in vivo neutralization of IFN-gamma resulted in a significant reduction of gastric inflammation in H. felis-infected, as well as immunized/challenged, mice. This treatment also revealed the presence of Th2 cells, restricted to immunized/challenged mice, as demonstrated by local and systemic production of IL-4 in these mice. These data demonstrate that Helicobacter infection and/or immunization stimulate a predominantly Th1-type, Ag-specific response and promote a local delayed-type hypersensitivity response in the stomach that may be inhibited by depletion of IFN-gamma.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mohammadi
authors.forename: S
authors.initials: S
authors.lastname: Czinn
authors.forename: R
authors.initials: R
authors.lastname: Redline
authors.forename: J
authors.initials: J
authors.lastname: Nedrud
mesh_terms: D000818:Animals; D005260:Female; D005756:Gastritis / Q000276:immunology; D016998:Helicobacter / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013270:Stomach / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014510:Urease / Q000276:immunology
chemical_list: D007371:Interferon-gamma; D014510:Urease