Bryan McDonald, Brent Y Chick, Diana C Hargreaves, Susan M Kaech
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引用次数: 0
摘要
T 细胞在受到 T 细胞受体刺激后的数天内会发生广泛的染色质重塑。然而,关于 T 细胞启动后 24 小时内早期重塑事件的动力学和目标基因位点以协调效应物分化的情况还没有很好的描述。我们发现,在刺激幼稚 CD8+ T 细胞的 1 小时内,染色质可及性被迅速、广泛地重塑,导致许多效应 T 细胞相关基因的全局染色质可及性增加,这些基因富含 AP-1、早期生长应答(EGR)和活化 T 细胞核因子(NFAT)结合位点,但这种短时间的刺激不足以导致体内克隆扩增。持续 24 小时的刺激会导致染色质进一步重塑,并足以实现克隆扩增。这些数据表明,抗原受体信号转导的持续时间与染色质重塑和效应细胞分化相关基因的激活密切相关,并强调了一种帮助 CD8+ T 细胞区分外来抗原和自身抗原的潜在机制。
Early Chromatin Remodeling Events in Acutely Stimulated CD8+ T Cells.
T cells undergo extensive chromatin remodeling over several days following stimulation through the T cell receptor. However, the kinetics and gene loci targeted by early remodeling events within the first 24 hours of T cell priming to orchestrate effector differentiation have not been well described. We identified that chromatin accessibility is rapidly and extensively remodeled within 1 hour of stimulation of naïve CD8+ T cells, leading to increased global chromatin accessibility at many effector T cell-associated genes that are enriched for AP-1, early growth response (EGR), and nuclear factor of activated T cells (NFAT) binding sites, but this short duration of stimulation is insufficient for commitment to clonal expansion in vivo. Sustained 24-hour stimulation led to further chromatin remodeling and was sufficient to enable clonal expansion. These data suggest that the duration of antigen receptor signaling is intimately coupled to chromatin remodeling and activation of genes involved in effector cell differentiation and highlight a potential mechanism that helps CD8+ T cells discriminate between foreign- and self-antigens.
期刊介绍:
The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.