Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics

Macaubas, C., Lee, P.T., Smallacombe, T.B., Holt, B.J., Wee, C., Sly, P.D. and Holt, P.G. (2002) Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics. Clinical and Experimental Allergy, 32 1: 97-106. doi:10.1046/j.0022-0477.2001.01288.x


Author Macaubas, C.
Lee, P.T.
Smallacombe, T.B.
Holt, B.J.
Wee, C.
Sly, P.D.
Holt, P.G.
Title Reciprocal patterns of allergen-induced GATA-3 expression in peripheral blood mononuclear cells from atopics vs. non-atopics
Journal name Clinical and Experimental Allergy   Check publisher's open access policy
ISSN 0954-7894
1365-2222
Publication date 2002-01
Sub-type Article (original research)
DOI 10.1046/j.0022-0477.2001.01288.x
Volume 32
Issue 1
Start page 97
End page 106
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell
Language eng
Formatted abstract
Background:
T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of individual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes.

Objective:

To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization.

Methods:

PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR.

Results:
We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation.

Conclusion:
These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.
Keyword Atopy
Th1/Th2
Transcription factors
GATA-3
c-Maf
Allergen
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 17 Nov 2010, 11:37:58 EST