title: GATA-3 in human T cell helper type 2 development.
abstract: 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.
authors.affiliation: Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group III, University of Erlangen-Nuremberg, 91054, Germany.
authors.forename: Alla
authors.initials: A
authors.lastname: Skapenko
authors.forename: Jan
authors.initials: J
authors.lastname: Leipe
authors.forename: Uwe
authors.initials: U
authors.lastname: Niesner
authors.forename: Koen
authors.initials: K
authors.lastname: Devriendt
authors.forename: Rolf
authors.initials: R
authors.lastname: Beetz
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Kalden
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Hendrik
authors.initials: H
authors.lastname: Schulze-Koops
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D005260:Female; D050990:GATA3 Transcription Factor; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D016335:Zinc Fingers
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015534:Trans-Activators