TGF-beta 1 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 do wn-regulated Th2 development of naive CD4(+) Mel-14(high) T cells derived f rom the DO11.10 ovalbumin-specific TCR-transgenic mouse, and this was obser ved both in cultures driven with anti-CD3 and anti-CD28 and with splenic AP C 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 i nhibits Th2 development via a STAT6-independent mechanism.