Nature Immunology
3, 549 - 557 (2002)
Published online: 13 May 2002; | doi:10.1038/ni794
T-bet is a STAT1-induced regulator of IL-12R expression in naïve
CD4+ T cellsMaryam Afkarian1, John R. Sedy1, Jianfei Yang1, Nils G. Jacobson1, Nezih Cereb2, Soo Y. Yang2, Theresa L. Murphy1
& Kenneth M. Murphy11
Department of Pathology and Immunology, Howard
Hughes Medical Institute, Washington University School of Medicine,
Box 8118, 660 S. Euclid Ave., St. Louis,
MO 63110, USA. 2
Histogenetics Inc. and Center for Genetic
Polymorphism, Hawthorne, NY 10532,
USA.
Correspondence should be addressed to Kenneth M. Murphy Murphy@immunology.wustl.eduT helper type 1 (TH1) cell development involves
interferon- (IFN-) signaling through signal transducer and
activator of transcription 1 (STAT1) and interleukin-12 (IL-12) signaling
through STAT4 activation. We examined here T-bet regulation and evaluated the
actions of T-bet in STAT1- and STAT4-dependent TH1 development
processes. We found that T-bet expression during T cell activation was strongly
dependent on IFN- signaling and STAT1 activation, but was independent of
STAT4. Ectopic T-bet expression strongly increased IFN- production in
TH2 cells activated by PMA-ionomycin, but weakly increased
IFN- production in TH2 cells stimulated by IL-12−IL-18
or OVA peptide−antigen-presenting cell stimulation. In contrast,
IL-12−IL-18−induced IFN- production remained STAT4-dependent
despite ectopic T-bet expression. Ectopic T-bet expression selectively induced
expression of IL-12R 2, but not IL-18R , in wild-type and
STAT1-/- TH2 cells, but did not
extinguish expression of GATA-3 and TH2 cytokines. Finally, ectopic
T-bet did not directly induce expression of endogenous T- bet independently of
IFN- or STAT1. Thus, T-bet is induced by IFN- and STAT1 signaling
during T cell activation. In addition, T-bet mediates STAT1-dependent processes
of TH1 development, including the induction of IL-12R2.
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