GATA-3 in Human T Cell Helper Type 2 Development

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 allel...

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Main Authors: Skapenko, Alla, Leipe, Jan, Niesner, Uwe, Devriendt, Koen, Beetz, Rolf, Radbruch, Andreas, Kalden, Joachim R., Lipsky, Peter E., Schulze-Koops, Hendrik
Format: Online
Language:English
Published: The Rockefeller University Press 2004
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211796/
id pubmed-2211796
recordtype oai_dc
spelling pubmed-22117962008-03-11 GATA-3 in Human T Cell Helper Type 2 Development Skapenko, Alla Leipe, Jan Niesner, Uwe Devriendt, Koen Beetz, Rolf Radbruch, Andreas Kalden, Joachim R. Lipsky, Peter E. Schulze-Koops, Hendrik Brief Definitive Report 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. The Rockefeller University Press 2004-02-02 /pmc/articles/PMC2211796/ /pubmed/14757746 http://dx.doi.org/10.1084/jem.20031323 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Skapenko, Alla
Leipe, Jan
Niesner, Uwe
Devriendt, Koen
Beetz, Rolf
Radbruch, Andreas
Kalden, Joachim R.
Lipsky, Peter E.
Schulze-Koops, Hendrik
spellingShingle Skapenko, Alla
Leipe, Jan
Niesner, Uwe
Devriendt, Koen
Beetz, Rolf
Radbruch, Andreas
Kalden, Joachim R.
Lipsky, Peter E.
Schulze-Koops, Hendrik
GATA-3 in Human T Cell Helper Type 2 Development
author_facet Skapenko, Alla
Leipe, Jan
Niesner, Uwe
Devriendt, Koen
Beetz, Rolf
Radbruch, Andreas
Kalden, Joachim R.
Lipsky, Peter E.
Schulze-Koops, Hendrik
author_sort Skapenko, Alla
title GATA-3 in Human T Cell Helper Type 2 Development
title_short GATA-3 in Human T Cell Helper Type 2 Development
title_full GATA-3 in Human T Cell Helper Type 2 Development
title_fullStr GATA-3 in Human T Cell Helper Type 2 Development
title_full_unstemmed GATA-3 in Human T Cell Helper Type 2 Development
title_sort gata-3 in human t cell helper type 2 development
description 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.
publisher The Rockefeller University Press
publishDate 2004
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211796/
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