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Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci

Genes & Immunity volume 8, pages 613–618 (2007)Cite this article

Abstract

Anergy is an important mechanism of peripheral tolerance in which T cells lose the capacity to produce proinflammatory cytokines such as interleukin-2 (IL-2) and interferon-γ (IFNγ). To determine whether the induction of T-cell anergy in vivo is associated with epigenetic changes that oppose cytokine gene expression, we measured DNA methylation and histone acetylation at the IL2 and IFNγ loci in CD4+T cells from mice tolerant to a viral superantigen. Tolerant T cells exhibited more DNA methylation and less histone acetylation at the regulatory regions of the IL2 and IFNγ genes than effector T cells, which are able to produce IL-2 and IFNγ. These data show that T-cell anergy in this model is associated with epigenetic modifications that oppose gene expression, and suggest that these mechanisms may be important in the maintenance of tolerance.

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Acknowledgements

We thank M Greene, B Li and C Chen for helpful discussions. These studies were supported by the Fred and Suzanne Biesecker Pediatric Liver Center and NIH Grant AI059881 to AW.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    R M Thomas & A D Wells

  2. Department of Pathology and Laboratory Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    S J Saouaf & A D Wells

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  1. R M Thomas
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  2. S J Saouaf
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  3. A D Wells
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Correspondence to A D Wells.

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Thomas, R., Saouaf, S. & Wells, A. Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci. Genes Immun 8, 613–618 (2007). https://doi.org/10.1038/sj.gene.6364415

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  • DOI: https://doi.org/10.1038/sj.gene.6364415

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