This study investigates the role of interferon γ (IFN-γ) in protective immunity against *Mycobacterium tuberculosis* (Mtb) infection in mice. The researchers found that mice with a disrupted *IFN-γ* gene were unable to control a normally sublethal dose of Mtb, leading to disseminated disease characterized by widespread tissue destruction and necrosis. Despite this, some delayed-type hypersensitivity (DTH)-like reactivity was still observed, suggesting that IFN-γ is essential for protective cellular immunity but not for DTH expression. The study also highlights the potential of IFN-γ knockout mice as a valuable model for evaluating therapeutic interventions in immunocompromised hosts. The findings provide insights into the complex mechanisms of protective immunity and the role of cytokines in host defense against Mtb infection.This study investigates the role of interferon γ (IFN-γ) in protective immunity against *Mycobacterium tuberculosis* (Mtb) infection in mice. The researchers found that mice with a disrupted *IFN-γ* gene were unable to control a normally sublethal dose of Mtb, leading to disseminated disease characterized by widespread tissue destruction and necrosis. Despite this, some delayed-type hypersensitivity (DTH)-like reactivity was still observed, suggesting that IFN-γ is essential for protective cellular immunity but not for DTH expression. The study also highlights the potential of IFN-γ knockout mice as a valuable model for evaluating therapeutic interventions in immunocompromised hosts. The findings provide insights into the complex mechanisms of protective immunity and the role of cytokines in host defense against Mtb infection.