Divisions of Allergy &Immunology and Human Genetics, Cincinnati Children's Hospital Medical Center and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, 45229, USA.
Department of Environmental Medicine, New York University School of Medicine, NY, 10987, USA.
Sci Rep. 2017 Jan 5;7:39785. doi: 10.1038/srep39785.
Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory.
尽管 T 细胞受体 (TCR) 刺激与共刺激一起足以激活幼稚 T 细胞和记忆 T 细胞，但记忆 T 细胞能够比幼稚 T 细胞更快地产生谱系特异性细胞因子。这种记忆细胞快速召回反应的机制尚未完全理解。在这里，我们使用 ChIP-Seq 对人类静止的幼稚、中央和效应记忆 T 细胞进行了表观遗传分析，发现与幼稚细胞不同，记忆 T 细胞中的细胞因子基因的调节元件即使在静止状态下也被激活的组蛋白修饰标记。因此，在激活时诱导快速召回基因表达的能力与记忆 T 细胞分化过程中阳性组蛋白修饰的沉积有关。我们提出了一种 T 细胞记忆模型，其中免疫记忆状态通过启动和转录记忆在表观遗传学上进行编码。
