Defective IL-2-mediated IL-2 receptor alpha chain expression in Stat3-deficient T lymphocytes.
Stat3, a member of signal transducers and activators of transcription (STAT), is activated by a variety of cytokines. Recently, mice lacking Stat3 specifically in T cells have been generated and shown to be defective in IL-6-induced proliferation due to the impairment in IL-6-mediated prevention of apoptosis. In the present study, we show that Stat3-deficient T cells are partially defective in IL-2-induced proliferation. Stat3-deficient T cells show impaired IL-2-mediated IL-2 receptor (IL-2R) alpha chain expression. When Stat3-deficient T cells are stimulated with high-dose IL-2, these T cells express IL-2Ralpha and proliferate to similar extents as wild-type T cells. These demonstrate that Stat3 activation is required for efficient T cell proliferation by IL-2 through IL-2Ralpha induction. Taken together, these findings demonstrate that Stat3 activation in T cells is responsible for IL-2- and IL-6-induced proliferation through distinct mechanisms.
Akaishi
H
H
Department of Biochemistry, Hyogo College of Medicine, Nishinomiya, Japan.
Takeda
K
K
Kaisho
T
T
Shineha
R
R
Satomi
S
S
Takeda
J
J
Akira
S
S
D000818:Animals; D017209:Apoptosis; D004268:DNA-Binding Proteins / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008894:Milk Proteins; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D008894:Milk Proteins; D015375:Receptors, Interleukin-2; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators