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 (beta2-chain; IL-12Rbeta2) 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.
IRCCS Salvatore Maugeri Foundation, Pavia, Italy.
E
E
Lantelme
S
S
Mantovani
B
B
Palermo
R
R
Campanelli
F
F
Sallusto
C
C
Giachino
D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D008213:Lymphocyte Activation / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D016335:Zinc Fingers / Q000276:immunology
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018121:Receptors, Cytokine; D015534:Trans-Activators