Stat5b is essential for natural killer cell-mediated proliferation and cytolytic activity

We have analyzed the immune system in Stat5-deficient mice. Although Stat5a (-/-) splenocytes have a partial defect in anti-CD3-induced proliferation t hat can be overcome by high dose interleukin (IL)-2, we now demonstrate tha t defective proliferation in Stat5b(-/-) splenocytes cannot be corrected by this treatment. Interestingly, this finding may be at least partially expl ained by diminished expression of the IL-2 receptor beta chain (IL-2R beta) , which is a component of the receptors for both IL-2 and IL-15, although o ther defects may also exist. Similar to the defect in proliferation ill act ivated splenocytes, freshly isolated splenocytes from Stat5b(-/-) mice exhi bited greatly diminished proliferation ill response to IL-2 and IL-15. This results from both a decrease in the number and responsiveness of natural k iller (NK) cells. Corresponding to the diminished proliferation, basal as w ell as IL-2- and IL-15-mediated boosting of NK cytolytic activity was also greatly diminished. These data indicate an essential nonredundant role for Stat5b for potent NK cell-mediated proliferation and cytolytic activity.