GATA-3 in Human T Cell Helper Type 2 Development

Skapenko A, Leipe J, Niesner U, Devriendt K, Beetz R, Radbruch A, Kalden JR, Lipsky PE and Schulze-Koops H
Source: J Exp Med
Publication Date: (2004)
Issue: 199(3): 423-428
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human peripheral blood unstim.
Species: human
Tissue Origin: blood
In primary memory CD4 T cells, protein expression of GATA-3 was reduced by nucleofection with a corresponding siRNA construct. Then, cells were cultured under Th2-inducing conditions. A significantly reduced Th2 cell differentiation was observed, indicating a dominant role of GATA-3 for this process.
The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell-mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3(+/-) individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell-mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3(+/+) controls. Concordant with these data, silencing of GATA-3 in GATA-3(+/+) CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo.