Interferon γ eliminates responding CD4 T cells during mycobacterial infection by inducing apoptosis of activated CD4 T cells

In Mycobacterium bovis Bacille Calmette-Guerin (BCG)-infected wild-type mice, there was a large expansion of an activated (CD44(hi)) splenic CD4 T cell population followed by a rapid contraction of this population to normal numbers. Contraction of the activated CD4 T cell population in wild-type mice was associated with increased apoptosis of activated CD4 T cells. In BCG- infected interferon (IFN)-γ knockout (KO) mice, the activated CD4 T cell population did not undergo apoptosis. These mice accumulated large numbers of CD4⁺CD44(hi) T cells that were responsive to mycobacterial antigens. Addition of IFN-γ to cultured splenocytes from BCG-infected IFN-γ KO mice induced apoptosis of activated CD4 T cells. IFN-γ-mediated apoptosis was abolished by depleting adherent cells or Mac-1⁺ spleen cells or by inhibiting nitric oxide synthase. Thus, IFN-γ is essential to a regulatory mechanism that eliminates activated CD4 T cells and maintains CD4 T cell homeostasis during an immune response.