The role of T cell subsets and cytokines in the pathogenesis of Helicobacter pylori gastritis in mice

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 i mmunopathogenesis of H. pylori-induced gastritis and delayed-type hypersens itivity (DTH) in mice. C57BL/6-Prkd(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 fro m C57BL/6(IFN-gamma-/-) or C57BL/6(IL-10-/-) mice. Four or eight weeks afte r transfer, DTH to H. pylori Ags was determined by footpad injection; gastr itis 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(+) splenocyte s, 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. Gast ritis was most severe in recipients of splenocytes from IL-10-deficient mic e, and least severe in those given IFN-gamma -deficient splenocytes. Bacter ial colonization in all groups was inversely correlated with gastritis. The se data indicate that 1) CD4(+) T cells are both necessary and sufficient f or 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 contribu tes 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.