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Eur J Immunol. 2000 Sep;30(9):2639-49.

TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression.

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1
Department of Immunology, DNAX Research Institute, Palo Alto, USA.

Abstract

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.

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