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

被引:225
作者
Eaton, KA [1 ]
Mefford, M [1 ]
Thevenot, T [1 ]
机构
[1] Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA
关键词
D O I
10.4049/jimmunol.166.12.7456
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-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 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.
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页码:7456 / 7461
页数:6
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