AN ESSENTIAL ROLE FOR ENDOGENOUS INTERFERON-GAMMA IN THE GENERATION OF PROTECTIVE T-CELLS AGAINST MYCOBACTERIUM-BOVIS BCG IN MICE

Protective CD4(+) T cells against Mycobacterium bovis bacillus Calmett e-Guerin (BCG), which are characterized by the ability to produce inte rferon-gamma (IFN-gamma), could be induced by immunization of mice wit h viable BCG but not with killed BCG. A high level of IFN-gamma mRNA w as observed when normal spleen cells were stimulated with viable bur n ot killed BCG. By comparing mice immunized with either viable or kille d M. bovis BCG, it was found that a high level of IFN-gamma mRNA was e xpressed only after immunization with viable BCG. This finding prompte d us to investigate the effect of neutralizing the IFN-gamma on the fi nal generation of protective T cells against M. bovis BCG. When endoge nous IFN-gamma was neutralized by administration of anti-IFN-gamma mon oclonal antibody in mice immunized with viable BCG, the generation of protective T cells was significantly impaired, as revealed by the adop tive transfer of spleen T cells. The generation of BCG-specific, IFN-g amma-producing T cells was also abolished. These results clearly demon strate that endogenous IFN-gamma actually plays a critical role in the generation of protective T cells against M. bovis BCG in vivo. Moreov er, this study suggests that the lack of IFN-gamma-inducing ability is responsible for the inability of killed M. bovis BCG to induce protec tive T cells in mice.