The objective of this study was to characterize the immune response induced by a live attenuated Salmonella Enteritidis (SE; ade(-)/his(-)) vaccine using an intraperitoneal immunization/challenge model in susceptible wild-type and cytokine-deficient BALB/c mice. In wild-type mice, inoculation of the SE live vaccine induced a protective immune response characterized by both cellular (production of interleukin(IL)-12 and interferon(IFN)-gamma, granuloma formation in liver and spleen, DTH response) and humoral effector mechanisms (high antigen-specific IgG2a titers). IL-12- and IL-4-deficient mice were immunized to study the individual roles of Th1 and Th2 cells, respectively. Protective immunity in wild-type mice required inoculation of >5 x 10(3)CFU of the attenuated live SE vaccine strain used. While IL-4-deficient mice developed a protective immune response similar to that found in wild-type mice, it was not possible to induce protective immunity in the highly susceptible IL-12-deficient mice due to severe disease symptoms and death following inoculation of the SE vaccine strain (doses >or=5 x 10(2)CFU were lethal for IL-12-deficient mice). Interestingly, persistence of the vaccine strain was observed in IL-4-deficient mice, indicating a role of IL-4 for clearance which, however, did not interfere with protective immunity. Together, the data indicate that the SE live vaccine activates a cellular and a humoral immune response, which are both regulated by Th1 cells via the secretion of IFN-gamma, whereas Th2 cells did not contribute essentially to the SE live-vaccine-induced immunity.