[PDF][PDF] An indirect effect of Stat5a in IL-2–induced proliferation: a critical role for Stat5a in IL-2–mediated IL-2 receptor α chain induction

H Nakajima, XW Liu, A Wynshaw-Boris, LA Rosenthal… - Immunity, 1997 - cell.com
H Nakajima, XW Liu, A Wynshaw-Boris, LA Rosenthal, K Imada, DS Finbloom…
Immunity, 1997cell.com
Stat5a was identified as a prolactin-induced transcription factor but also is activated by other
cytokines, including interleukin-2 (IL-2) and IL-7. We have now analyzed the immune system
of Stat5a-deficient mice. Stat5a−/− splenocytes exhibited defective IL-2–induced expression
of the IL-2 receptor α chain (IL-2Rα), a protein that together with IL-2Rβ and the common
cytokine receptor γ chain (γ c) mediates high-affinity IL-2 binding. Correspondingly,
Stat5a−/− splenocytes exhibited markedly decreased proliferation to IL-2, although maximal …
Abstract
Stat5a was identified as a prolactin-induced transcription factor but also is activated by other cytokines, including interleukin-2 (IL-2) and IL-7. We have now analyzed the immune system of Stat5a-deficient mice. Stat5a−/− splenocytes exhibited defective IL-2–induced expression of the IL-2 receptor α chain (IL-2Rα), a protein that together with IL-2Rβ and the common cytokine receptor γ chain (γc) mediates high-affinity IL-2 binding. Correspondingly, Stat5a−/− splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2Rβ/γc receptors. Thus, defective Stat5a expression results in diminished proliferation by an indirect mechanism, resulting from defective receptor expression. Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2–induced IL-2Rα expression.
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