功能和表观遗传学研究揭示了体外生成和体内衍生滤泡辅助 T 细胞的多步分化和可塑性。
Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells.
机构信息
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Immunity. 2011 Oct 28;35(4):622-32. doi: 10.1016/j.immuni.2011.07.015. Epub 2011 Oct 20.
Abstract
Follicular T helper (Tfh) cells provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated protein (SAP) prevent GC formation because of defective T cell-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally competent "Tfh-like" cells that expressed interleukin-21, Tfh cell markers, and Bcl6 and rescued GC formation in SAP-deficient hosts better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wild-type, yet failed to support GCs in vivo. Interestingly, both Tfh-like and in vivo-derived Tfh cells could produce effector cytokines in response to polarizing conditions. Moreover, Th1, Th2, and Th17 cells could be reprogrammed to obtain Tfh cell characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations.
摘要
滤泡辅助性 T 细胞（Tfh）为生发中心（GC）的形成提供了关键的 B 细胞辅助。影响信号淋巴细胞激活分子相关蛋白（SAP）的突变会导致 GC 形成缺陷，因为 T 细胞-B 细胞相互作用受损，但 Tfh 细胞分化的影响仍不清楚。我们描述了功能性“Tfh 样”细胞的体外分化，这些细胞表达白细胞介素 21、Tfh 细胞标记物和 Bcl6，并且比其他辅助性 T（Th）细胞更好地挽救了 SAP 缺陷型宿主中的 GC 形成。SAP 缺陷型 Tfh 样细胞与野生型细胞几乎无法区分，但在体内无法支持 GC 的形成。有趣的是，Tfh 样细胞和体内衍生的 Tfh 细胞都可以对极化条件产生效应细胞因子。此外，Th1、Th2 和 Th17 细胞可以被重新编程以获得 Tfh 细胞特征。ChIP-Seq 分析显示 Tfh 样细胞和体外 Tfh 细胞中的 Tbx21、Gata3 和 Rorc 以及非 Tfh 细胞中的 Bcl6 上存在阳性表观遗传标记，支持 Tfh 和其他 Th 细胞群之间的可塑性概念。
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