Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci.
Superantigen-induced CD4+ T cell tolerance is associated with DNA methylation and histone hypo-acetylation at cytokine gene loci.
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超抗原诱导的 CD4 T 细胞耐受与细胞因子基因位点的 DNA 甲基化和组蛋白低乙酰化有关。
DOI：
10.1038/sj.gene.6364415
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发表时间：
2007
影响因子：
5
通讯作者：
Wells,AD
中科院分区：
文献类型：
--
作者：
Thomas,RM;Saouaf,SJ;Wells,AD
无能是外周耐受的一个重要机制，T细胞失去产生促炎细胞因子的能力，如白介素2(IL-2)和干扰素-γ(干扰素γ)。为了确定体内T细胞无能的诱导是否与反对细胞因子基因表达的表观遗传变化有关，我们检测了对病毒超抗原耐受的小鼠CD_4+T细胞中IL_2和干扰素γ位点的DNA甲基化和组蛋白乙酰化。与能够产生IL-2和干扰素γ的效应性T细胞相比，耐受性T细胞在IL-2和干扰素γ基因的调控区有更多的DNA甲基化和更少的组蛋白乙酰化。这些数据表明，在这个模型中，T细胞无能与反对基因表达的表观遗传修饰有关，并表明这些机制可能在维持耐受中起重要作用。
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.