An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction.
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 alpha chain (IL-2R alpha), a protein that together with IL-2R beta and the common cytokine receptor gamma chain (gamma(c)) 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-2R beta/gamma(c) 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-2R alpha expression.
Nakajima
H
H
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Liu
X W
XW
Wynshaw-Boris
A
A
Rosenthal
L A
LA
Imada
K
K
Finbloom
D S
DS
Hennighausen
L
L
Leonard
W J
WJ
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004768:Enterotoxins / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000502:physiology*; D015851:Interleukin-7 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D015534:Trans-Activators / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D004268:DNA-Binding Proteins; D004768:Enterotoxins; D005938:Glucocorticoids; D007376:Interleukin-2; D015851:Interleukin-7; D008894:Milk Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; C494093:Stat5a protein, mouse; D015534:Trans-Activators; D019014:fas Receptor; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone