Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation

IL-4 is important in Th2 differentiation and in cell expansion. Stat6 is necessary and sufficient for both functions. Although Gata3 is critical for Th2 polarization, it is not sufficient to mediate IL-4-driven cell expansion. We report that growth factor independent-1 (Gfi-1), a Stat6-dependent transcriptional repressor, strikingly increases Th2 cell expansion by promoting proliferation and preventing apoptosis. Cells infected with a Gfi-1 retrovirus show striking enhancement of IL-2-induced Stat5 phosphorylation and repression of p27(Kip-1) expression, suggesting a potential mechanism for the Gfi-1 growth effect. The synergy of Gfi-1 and Gata3 provides a mechanism through which IL-4 could selectively promote Th2 cell expansion.