BACKGROUND: In contrast to wild type, interleukin-10-deficient (IL-10(-/-)) mice are able to clear Helicobacter infection. In this study, we investigated the immune response of IL-10(-/-) mice leading to the reduction of Helicobacter infection. MATERIALS AND METHODS: We characterized the immune responses of Helicobacter felis-infected IL-10(-/-) mice by studying the systemic antibody and cellular responses toward Helicobacter. We investigated the role of CD4(+) T cells in the Helicobacter clearance by injecting H. felis-infected IL-10(-/-) mice with anti-CD4 depleting antibodies. To examine the role of mast cells in Helicobacter clearance, we constructed and infected mast cells and IL-10 double-deficient mice. RESULTS: Reduction of Helicobacter infection in IL-10(-/-) mice is associated with strong humoral (fivefold higher serum antiurease antibody titers were measured in IL-10(-/-) in comparison to wild-type mice, p < .008) and cellular (urease-stimulated splenic CD4(+) T cells isolated from infected IL-10(-/-) mice produce 150-fold more interferon-gamma in comparison to wild-type counterparts, p < .008) immune responses directed toward Helicobacter. Depletion of CD4(+) cells from Helicobacter-infected IL-10(-/-) mice lead to the loss of bacterial clearance (rapid urease tests are threefold higher in CD4(+) depleted IL-10(-/-) in comparison to nondepleted IL-10(-/-) mice, p < .02). Mast cell IL-10(-/-) double-deficient mice clear H. felis infection, indicating that mast cells are unnecessary for the bacterial eradication in IL-10(-/-) mice. CONCLUSION: Taken together, these results suggest that CD4(+) cells are required for Helicobacter clearance in IL-10(-/-) mice. This reduction of Helicobacter infection is, however, not dependent on the mast cell population.