A unique DNA methylation signature defines a population of IFN-γ/IL-4 double-positive T cells during helminth infection.
Bottom Line: 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.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.
Affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.Show MeSH
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Mentions: In order to examine DNA methylation in an in vivo infection setting we isolated splenic CD4+ T cells from mice that had been infected with S. mansoni for 8 weeks and from age-matched uninfected controls (Fig.1A). A marked proportion of CD4+ T cells displayed properties of both Th1 and Th2 cells in that they simultaneously made both IFN-γ and IL-4 8 (Fig.1B and Supporting Information Fig. 1). Conventional IFN-γ+IL-4− Th1 cells and IFN-γ−IL-4+ Th2 cells were also present, consistent with previous reports 18,19 and CD4+ T cells from uninfected mice showed significantly less expression of IFN-γ or IL-4 (Fig.1B). IFN-γ+IL-4+ cells were observed in five separate S. mansoni infections with the proportion varying from approximately 2–9% of CD4+ T cells (data not shown), demonstrating that IFN-γ+IL-4+ cells can be found in the spleen in a Th2-dominated infection setting.
Affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.