Are Stat5a and Stat5b functionally redundant in the immune system?
The biological significance of Stat5 proteins in IL-2 signaling is further established from analyses of gene-targeted mice that lack expression of Stat5 proteins. Originally, Stat5a was discovered as a mammary gland factor and indeed Stat5a-/- mice exhibit a profound defect in adult mammary gland development and lactogenesis (Liu et al., 1997). On the other hand, Stat5b-/- mice develop the defects related to the growth hormone actions (Udy et al., 1997). However, both types of the knockout mice additionally exhibit marked defects in the immune responses. In Stat5a-/- mice, there is a defect in IL-2-induced IL-2R expression (Nakajima et al., 1997). Consistent with this observation, splenocytes from Stat5a-/- mice exhibit markedly decreased proliferation to low concentrations of IL-2, although maximal proliferation is still achieved at concentrations of IL-2 high enough to titrate intermediate affinity IL-2R/c receptors. This defect also correlates with defective V8+CD8+ T-cell expansion
