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The Journal of Immunology, 2001, 166: 7456-7461.
Copyright © 2001 by The American Association of Immunologists

The Role of T Cell Subsets and Cytokines in the Pathogenesis of Helicobacter pylori Gastritis in Mice1

Kathryn A. Eaton2, Megan Mefford and Tracy Thevenot

Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210

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-Prkdcscid mice were infected with H. pylori and reconstituted with CD4+, CD4-depleted, CD4+CD45RBhigh, or CD4+CD45RBlow splenocytes from wild-type C57BL/6 mice or with splenocytes from C57BL/6IFN-{gamma}-/- or C57BL/6IL-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+CD45RBhigh 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.




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