AN ESSENTIAL ROLE FOR INTERFERON-GAMMA IN RESISTANCE TO MYCOBACTERIUM-TUBERCULOSIS INFECTION

Tuberculosis, a major health problem in developing countries, has reem erged in recent years in many industrialized countries. The increased susceptibility of immunocompromised individuals to tuberculosis, and m any experimental studies indicate that T cell-mediated immunity plays an important role in resistance. The lymphokine interferon gamma (IFN- gamma) is thought to be a principal mediator of macrophage activation and resistance to intracellular pathogens. Mice have been developed wh ich fail to produce IFN-gamma (gko), because of a targeted disruption of the gene for IFN-gamma. Upon infection with Mycobacterium tuberculo sis, although they develop granulomas, gko mice fail to produce reacti ve nitrogen intermediates and are unable to restrict the growth of the bacilli. In contrast to control mice, gko mice exhibit heightened tis sue necrosis and succumb to a rapid and fatal course of tuberculosis t hat could be delayed, but not prevented, by treatment with exogenous r ecombinant IFN-gamma.