The Role of T Cell Subsets and Cytokines in the Pathogenesis ofHelicobacter pyloriGastritis in Mice

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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-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-γ−/− 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-γ 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-γ secretion in response to H. pylori Ags was correlated with gastritis, although splenocytes from all groups of mice secreted some IFN-γ. Gastritis was most severe in recipients of splenocytes from IL-10-deficient mice, and least severe in those given IFN-γ-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-γ contributes to gastritis and IL-10 suppresses it, but IFN-γ 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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