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Kinetics of GATA‐3 gene expression in early polarizing and committed human T cells

Different transcription factors have been shown to control the transition of naive T cells into T helper 1 (Th1)/Th2 subsets. The T‐cell‐specific transcription factor GATA‐3 is known to be selectively expressed in murine developing Th2 cells and to exert a positive action on Th2‐specific cytokine production. Investigating GATA‐3 gene regulation in human T cells we have found that naive T cells highly express GATA‐3, and during early T2 or T1 polarization, respectively, they either maintain or quickly down‐regulate expression. In developing T2 cells, as well as in committed Th2 cell lines and clones, we found a positive correlation among GATA‐3, interleukin (IL)‐5 and IL‐4 gene expression kinetics, supporting the positive action of GATA‐3 on Th2‐specific cytokine production. A possible relationship between GATA‐3 gene expression and the down‐regulation of the IL‐12 receptor (β2‐chain; IL‐12Rβ2) gene was evident only in the early phases of T2 polarization (within 24 hr), and not demonstrated at later times. During T‐cell commitment the presence of IL‐4 in the culture was essential to maintain or enhance GATA‐3 transcription, while IL‐12 was not necessary for full repression of GATA‐3. Finally, we showed selective GATA‐3 up‐regulation in human Th2 cell lines and clones and the maintainance of a low basal level of GATA‐3 expression in Th1 cells upon activation.