TGF- beta 1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression

• Published in: European journal of immunology Vol. 30; no. 9; pp. 2639 - 2649
• Main Authors: Heath, V L, Murphy, EE, Crain, C, Tomlinson, M G, O'Garra, A
• Format: Journal Article
• Language: English
• Published: 01-09-2000
• Subjects: GATA-3 protein; Stat6 protein; transforming growth factor-^b1
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200009)30:9<2639::AID-IMMU2639>3.0.CO;2-7

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 super(+) Mel-14 super(high) 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.