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.