Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-γ-dominant versus an IL-4-dominant immune response

Abstract

The mechanisms responsible for differential commitment of effector T cells to the production of either the IL-4/5/10 group or to the IL-2/IFN-_γ group of lymphokines during an immune response have not yet been clearly elucidated. We have used Salmonella typhimurium as a model murine bacterial parasite in BALB/c mice for live-cell versus killed-cell immunization and looked at the immune response in terms of delayed type hypersensitivity (DTH), IgG subclass distribution in the serum antibody response, and antigen-specific T cell proliferation and lymphokine secretion. The results indicate that the two forms of immunogen induce qualitatively different immune responses. Intraperitoneal immunization with live bacteria induces an IFN-_γ-dominant immune response associated with a strong DTH reaction and relatively higher levels of specific antibodies belonging to the IFN-_γ-dependent IgG2a isotype rather than the IL-4-dependent IgG1 isotype. Immunization with heat-killed bacteria gives rise to an IL-4-dominated response that shows excellent proliferatlve capacities in vitro, with lower levels of DTH responses and comparatively high levels of specific antibodies of the IgG1 isotype. IL-2 production in the responses generated by the two modes of immunization, however, is not preferentially associated with IFN-_γ production, unlike the reported profiles of long-lived murine T cell clones in vitro.