Background: Although previous studies have reported important roles of CD4(+) type1-helper T cells and regulatory T cells in Helicobacter-associated gastritis, the significance of CD8(+) cytotoxic T cells remains unknown. To study the roles of CD8(+) T cells, we examined the immune response in the gastric mucosa of Helicobacter felis-infected major histocompatibility complex (MHC) class II-deficient (II-/-) mice, which lack CD4(+) T cells.
Materials and methods: Stomachs from H. felis-infected wild-type and infected MHC II-/- mice were examined histologically and immunohistochemically. Gastric acidity and serum levels of anti-H. felis antibodies were measured. The expression of pro-inflammatory and anti-inflammatory cytokine, Fas-ligand, perforin, and Foxp3 genes in the gastric mucosa was investigated.
Results: H. felis-infected MHC II-/- mice developed severe gastritis, accompanied by marked infiltration of CD8(+) cells. At 1 and 2 months after inoculation, mucosal inflammation and atrophy were more severe in MHC II-/- mice, although gastritis had reached similar advanced stages at 3 months after inoculation. There was little infiltration of CD4(+) cells, and no Foxp3-positive cells were detected in the gastric mucosa of the infected MHC II-/- mice. The expression of the interleukin-1 beta and Fas-ligand genes was up regulated, but that of Foxp3 was down regulated in the infected MHC II-/- mice. Serum levels of anti-H. felis antibodies were lower in the infected MHC II-/- mice, despite severe gastritis.
Conclusions: The present study suggests that cross-primed CD8(+) cytotoxic T cells can induce severe H.-associated gastritis in the absence of CD4(+) helper T cells and that Foxp3-positive cells may have an important role in the control of gastric inflammation.