Kinetics of GATA-3 gene expression in early polarizing and committed humanT cells

Different transcription factors have been shown to control the transition o f naive T cells into T helper 1 (Th1)/Th2 subsets. The T-cell-specific tran scription factor GATA-3 is known to be selectively expressed in murine deve loping Th2 cells and to exert a positive action on Th2-specific cytokine pr oduction. Investigating GATA-3 gene regulation in human T cells we have fou nd that naive T cells highly express GATA-3, and during early T2 or T1 pola rization. respectively, they either maintain or quickly down-regulate expre ssion. In developing T2 cells, as well as in committed Th2 cell lines acid clones, we found a positive correlation among GATA-3, interleukin (IL)-5 an d IL-4 gene expression kinetics, supporting the positive action of GATA-3 o n Th2-specific cytokine production. A possible relationship between GATA-3 gene expression and the down-regulation of the IL-12 receptor (beta2-chain, IL-12R beta2) gene was evident only in the early phases of T2 polarization (within 24 hr), and not demonstrated at later times. During T-cell commitm ent the presence of IL-4 in the culture was essential to maintain or enhanc e GATA-3 transcription, while IL-12 was not necessary for full repression o f GATA-3. Finally, we showed selective GATA-3 up-regulation in human Th2 ce ll lines and clones and the maintainance of a low basal level of GATA-3 exp ression in Th1 cells upon activation.