title: The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice.
abstract: Gastritis due to Helicobacter pylori in mice and humans is considered a Th1-mediated disease, but the specific cell subsets and cytokines involved are still not well understood. The goal of this study was to investigate the immunopathogenesis of H. pylori-induced gastritis and delayed-type hypersensitivity (DTH) in mice. C57BL/6-Prkdc(scid) mice were infected with H. pylori and reconstituted with CD4+, CD4-depleted, CD4+CD45RB(high), or CD4+CD45RB(low) splenocytes from wild-type C57BL/6 mice or with splenocytes from C57BL/6(IFN-gamma-/-) or C57BL/6(IL-10-/-) mice. Four or eight weeks after transfer, DTH to H. pylori Ags was determined by footpad injection; gastritis and bacterial colonization were quantified; and IFN-gamma secretion by splenocytes in response to H. pylori Ag was determined. Gastritis and DTH were present in recipients of unfractionated splenocytes, CD4+ splenocytes, and CD4+CD45RB(high) splenocytes, but absent in the other groups. IFN-gamma secretion in response to H. pylori Ags was correlated with gastritis, although splenocytes from all groups of mice secreted some IFN-gamma. Gastritis was most severe in recipients of splenocytes from IL-10-deficient mice, and least severe in those given IFN-gamma-deficient splenocytes. Bacterial colonization in all groups was inversely correlated with gastritis. These data indicate that 1) CD4+ T cells are both necessary and sufficient for gastritis and DTH due to H. pylori in mice; 2) high expression of CD45RB is a marker for gastritis-inducing CD4+ cells; and 3) IFN-gamma contributes to gastritis and IL-10 suppresses it, but IFN-gamma secretion alone is not sufficient to induce gastritis. The results support the assertion that H. pylori is mediated by a Th1-biased cellular immune response.
authors.affiliation: Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210, USA. eaton.1@osu.edu
authors.forename: K A
authors.initials: KA
authors.lastname: Eaton
authors.forename: M
authors.initials: M
authors.lastname: Mefford
authors.forename: T
authors.initials: T
authors.lastname: Thevenot
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005756:Gastritis / Q000209:etiology / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016481:Helicobacter Infections / Q000209:etiology / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000382:microbiology; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000637:transplantation
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D016753:Interleukin-10; D007371:Interferon-gamma