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CpG methylation patterns in the IFN γ promoter in naive T cells: Variations during Th1 and Th2 differentiation and between atopics and non‐atopics
Author(s) -
White Gregory P.,
Hollams Elysia M.,
Yerkovich Stephanie T.,
Bosco Anthony,
Holt Barbara J.,
Bassami Mohammad R.,
Kusel Merci,
Sly Peter D.,
Holt Patrick G.
Publication year - 2006
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/j.1399-3038.2006.00465.x
Subject(s) - atopy , cord blood , dna methylation , cpg site , immunology , methylation , cd8 , cytotoxic t cell , promoter , epigenetics , medicine , biology , microbiology and biotechnology , allergy , gene expression , gene , immune system , in vitro , genetics
Interferon‐ γ (IFN γ ) gene expression is tightly regulated in early life, and exaggerated negative control of IFN γ production in CD4 + T cells has been associated with risk for subsequent development of atopy. Recent studies have demonstrated hypermethylation of CpG sites in the IFN γ promoter in neonates, a mechanism which in mice leads to strong suppression of IFN γ gene transcription. In the present study, the methylation status of six CpG sites in the proximal promoter of the human IFN γ gene was determined by bisulphite sequencing. Cell populations studied were Th1 or Th2 polarized cell lines derived from neonatal and adult CD4 + /CD45RA + T cells, CD4 + and CD8 + naive T cells from cord blood of children followed to outcome age 2 for assessment of atopy status, and CD4 + and CD8 + naive T cells from 6 yr old and adult atopics and controls. We demonstrate that in vitro differentiation of CD4 + T cells down the Th1 pathway (but not the Th2 pathway) is accompanied by progressive demethylation of CpG sites in the IFN γ promoter, which is most marked in neonatal cells. Atopy development by age 2 was not associated with variations in methylation patterns in cord blood T cells. However, IFN γ promoter methylation was reduced in CD8 + T cells from atopic children in the age range in which hyperproduction of IFN γ as recently been identified as a common feature of the atopic phenotype. The findings demonstrate the potency of IFN γ promoter methylation as a mechanism for control of human IFN γ gene expression, particularly during early life. Differential regulation of IFN γ promoter methylation in T cells may be an important contributory factor in atopy development in childhood, and this possibility warrants further detailed investigation.