REQUIREMENT OF THE INITIAL PRODUCTION OF GAMMA-INTERFERON IN THE GENERATION OF PROTECTIVE IMMUNITY OF MICE AGAINST LISTERIA-MONOCYTOGENES

Protective immunity of mice against Listeria monocytogenes, which is m ediated mainly by gamma interferon (IFN-gamma)-producing T cells, was induced by immunization with viable bacteria but not with killed bacte ria, By comparing mice immunized with either viable or killed L. monoc ytogenes, it was found that IFN-gamma was produced al the initial stag e only after immunization with viable bacteria, This finding prompted us to investigate the effect of neutralizing the IFN-gamma on the fina l generation of protective T cells against L., monocytogenes. When end ogenous IFN-gamma was neutralized by administration of anti-IFN-gamma monoclonal antibody for the initial 2 days in mice immunized with viab le bacteria, the generation of protective T cells on day 6 was complet ely blocked, as revealed by T-cell adoptive transfer. The generation o f listeria-specific IFN-gamma-producing T cells mas also abolished. Th ese results clearly demonstrated that endogenous IFN-gamma, which is p roduced at the initial stage of immunization, actually plays a critica l role in the generation of protective T cells against L, monocytogene s in vivo. Moreover, this study suggested that the lack of IFN-gamma-i nducing ability is responsible for the inability of killed L, monocyto genes to induce protective T cells in mice.