TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression.
TGF-beta plays an important role in immune regulation in vivo and affects T cell differentiation in vitro. Here we describe how TGF-beta modulates Th2 development in vitro and investigate its mechanisms of action. TGF-beta down-regulated Th2 development of naive CD4+ Mel-14high T cells derived from the DO11.10 ovalbumin-specific TCR-transgenic mouse, and this was observed both in cultures driven with anti-CD3 and anti-CD28 and with splenic APC and antigen. TGF-beta down-regulated GATA-3 expression in developing Th2 and these cells showed a diminished IL-4-induced STAT6 activation. We found, however, that naive cells driven in Th2 conditions with TGF-beta did not show a significantly decreased STAT6 activation, suggesting that TGF-beta inhibits Th2 development via a STAT6-independent mechanism.
Heath
V L
VL
Department of Immunology, DNAX Research Institute, Palo Alto, USA.
Murphy
E E
EE
Crain
C
C
Tomlinson
M G
MG
O'Garra
A
A
D000818:Animals; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D050990:GATA3 Transcription Factor; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051257:Proto-Oncogene Proteins c-maf; D050800:STAT6 Transcription Factor; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology*; D015534:Trans-Activators / Q000096:biosynthesis* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C495608:Maf protein, mouse; D011518:Proto-Oncogene Proteins; D051257:Proto-Oncogene Proteins c-maf; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma