IMMUNIZATION WITH LIVE VERSUS KILLED SALMONELLA-TYPHIMURIUM LEADS TO THE GENERATION OF AN IFN-GAMMA-DOMINANT VERSUS AN IL-4-DOMINANT IMMUNE-RESPONSE

The mechanisms responsible for differential commitment of effector T c ells to the production of either the IL-4/5/10 group or to the IL-2/IF N-gamma group of lymphokines during an immune response have not yet be en clearly elucidated. We have used Salmonella typhimurium as a model murine bacterial parasite in BALB/c mice for live-cell versus killed-c ell immunization and looked at the immune response in terms of delayed type hypersensitivity (DTH), IgG subclass distribution in the serum a ntibody response, and antigen-specific T cell proliferation and lympho kine secretion. The results indicate that the two forms of immunogen i nduce qualitatively different immune responses. Intraperitoneal immuni zation with live bacteria induces an IFN-gamma-dominant immune respons e associated with a strong DTH reaction and relatively higher levels o f specific antibodies belonging to the IFN-gamma-dependent IgG2a isoty pe rather than the IL-4-dependent IgG1 isotype. Immunization with heat -killed bacteria gives rise to an IL-4-dominated response that shows e xcellent proliferative capacities in vitro, with lower levels of DTH r esponses and comparatively high levels of specific antibodies of the I gG1 isotype. IL-2 production in the responses generated by the two mod es of immunization, however, is not preferentially associated with IFN -gamma production, unlike the reported profiles of long-lived murine T cell clones in vitro.