Cutting edge:: Innate immune cells contribute to the IFN-γ-dependent regulation of antigen-specific CD8+ T cell homeostasis

IFN-gamma has a dual function in the regulation of T cell homeostasis. It promotes the expansion of effector T cells and simultaneously programs their contraction. The cellular mechanisms leading to this functional dichotomy of IFN-gamma have not been identified to date. In this study we show: 1) that expansion of wild-type CD8(+) T cells is defective in IFN-gamma-deficient mice but increased in IFN-gamma R-deficient mice; and 2) that contraction of the effector CD8(+) T cell pool is impaired in both mouse strains. Furthermore, we show that CD11b(+) cells responding to IFN-gamma are sufficient to limit CD8(+) T cell expansion and promote contraction. The data presented here reveal that IFN-gamma directly promotes CD8(+) T cell expansion and simultaneously induces suppressive functions in CD11b(+) cells that counter regulate CD8(+) T cell expansion, promote contraction, and limit memory formation. Thus, innate immune cells contribute to the IFN-gamma-dependent regulation of Ag-specific CD8(+) T cell homeostasis.