Clinical & Experimental Allergy

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

Authors

  • C. Macaubas,

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author
  • P. T. Lee,

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author
  • T. B. Smallacombe,

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author
  • B. J. Holt,

    Corresponding author
    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
      Professor P. G. Holt, Division of Cell Biology, TVW Telethon Institute for Child Health Research, PO Box855, West Perth WA 6872, Australia. E-mail: patrick@ichr.uwa.edu.au
    Search for more papers by this author
  • C. Wee,

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author
  • P. D. Sly,

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author
  • P. G. Holt

    1. TVW Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, Australia
    Search for more papers by this author

Professor P. G. Holt, Division of Cell Biology, TVW Telethon Institute for Child Health Research, PO Box855, West Perth WA 6872, Australia. E-mail: patrick@ichr.uwa.edu.au

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.

Ancillary