Requirement of the initial production of gamma interferon in the generation of protective immunity of mice against Listeria monocytogenes

Abstract

Protective immunity of mice against Listeria monocytogenes, which is mediated mainly by gamma interferon (IFN-gamma)-producing T cells, was induced by immunization with viable bacteria but not with killed bacteria. By comparing mice immunized with either viable or killed L. monocytogenes, it was found that IFN-gamma was produced at the initial stage only after immunization with viable bacteria. This finding prompted us to investigate the effect of neutralizing the IFN-gamma on the final generation of protective T cells against L. monocytogenes. When endogenous IFN-gamma was neutralized by administration of anti-IFN-gamma monoclonal antibody for the initial 2 days in mice immunized with viable bacteria, the generation of protective T cells on day 6 was completely blocked, as revealed by T-cell adoptive transfer. The generation of listeria-specific IFN-gamma-producing T cells was also abolished. These results clearly demonstrated that endogenous IFN-gamma, which is produced at the initial stage of immunization, actually plays a critical role in the generation of protective T cells against L. monocytogenes in vivo. Moreover, this study suggested that the lack of IFN-gamma-inducing ability is responsible for the inability of killed L. monocytogenes to induce protective T cells in mice.