title: A unique DNA methylation signature defines a population of IFN-γ/IL-4 double-positive T cells during helminth infection.
abstract: Th1 and Th2 cell fates are traditionally viewed as mutually exclusive, but recent work suggests that these lineages may be more plastic than previously thought. When isolating splenic CD4(+) T cells from mice infected with the parasitic helminth Schistosoma mansoni, we observed a defined population of IFN-γ/IL-4 double-positive cells. These IFN-γ(+) IL-4(+) cells showed differences in DNA methylation at the Ifng and Il4 loci when compared with IFN-γ(+) IL-4(-) (Th1) and IFN-γ(-) IL-4(+) (Th2) cells, demonstrating that they represent a distinct effector cell population. IFN-γ(+) IL-4(+) cells also displayed a discrete DNA methylation pattern at a CpG island within the body of the Gata3 gene, which encodes the master regulator of Th2 identity. DNA methylation at this region correlated with decreased Gata3 levels, suggesting a possible role in controlling Gata3 expression. These data provide important insight into the molecular mechanisms behind the co-existence of Th1 and Th2 characteristics.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Aimée M
authors.initials: AM
authors.lastname: Deaton
authors.forename: Peter C
authors.initials: PC
authors.lastname: Cook
authors.forename: Dina
authors.initials: D
authors.lastname: De Sousa
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Phythian-Adams
authors.forename: Adrian
authors.initials: A
authors.lastname: Bird
authors.forename: Andrew S
authors.initials: AS
authors.lastname: MacDonald
mesh_terms: D000818:Animals; D018899:CpG Islands / Q000276:immunology; D019175:DNA Methylation / Q000276:immunology*; D005260:Female; D050990:GATA3 Transcription Factor / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D051379:Mice; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: DNA methylation; Gata3; Helminth; Th1/Th2