Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells

Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mic e deficient in both genes lack all growth hormone and prolactin functions b ut retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to u ndergo cell cycle progression or to express genes controlling cell cycle pr ogression. In addition, the mice lack NK cells, develop splenomegaly, and h ave T cells with an activated phenotype, phenotypes seen in IL-2 receptor b eta chain-deficient mice. These phenotypes are not seen in mice lacking Sta t5a or Stat5b alone. The results demonstrate that the State proteins, redun dantly, are essential mediators of IL-2 signaling in T cells.