Regulation of IFN- gamma Signaling Is Essential for the Cytotoxic Activity of CD8 super(+) T Cells

Previous studies have demonstrated that, as naive murine CD4 super(+) cells differentiate into Th1 cells, they lose expression of the second chain of IFN- gamma R (IFN- gamma R2). Hence, the IFN- gamma -producing subset of Th cells is unresponsive to IFN- gamma . Analysis of IFN- gamma -producing CD8 super(+) T cells demonstrates that, like Th1 cells, these cells do not express IFN- gamma R2. To define the importance of IFN- gamma signaling for the development of functional CD8 super(+) T cells, mice either lacking IFN- gamma R2 or overexpressing this protein were examined. While CD8 super(+) T cell development and function appear normal in IFN- gamma R2 super(-/-) mice, CD8 super(+) T cell function in IFN- gamma R2 transgenic is altered. IFN- gamma R2 transgenic CD8 super(+) T cells are unable to lyse target cells in vitro. However, these cells produce Fas ligand, perforin, and granzyme B, the effector molecules required for killing. Interestingly, TG CD8 super(+) T cells proliferate normally and produce cytokines, such as IFN- gamma in response to antigenic stimulation. Therefore, although IFN- gamma signaling is not required for the generation of normal cytotoxic T cells, constitutive IFN- gamma signaling can selectively impair the cytotoxic function of CD8 super(+) T cells.