PDF(Pubmed)
Abstract：
UNASSIGNED: Follicular Lymphoma (FL) results from the malignant transformation of germinal center (GC) B cells. FL B cells display recurrent and diverse genetic alterations, some of them favoring their direct interaction with their cell microenvironment, including follicular helper T cells (Tfh). Although FL-Tfh key role is well-documented, the impact of their regulatory counterpart, the follicular regulatory T cell (Tfr) compartment, is still sparse.
UNASSIGNED: The aim of this study was to characterize FL-Tfr phenotype by cytometry, gene expression profile, FL-Tfr origin by transcriptomic analysis, and functionality by in vitro assays.
UNASSIGNED: CD4+CXCR5+CD25hiICOS+ FL-Tfr displayed a regulatory program that is close to classical regulatory T cell (Treg) program, at the transcriptomic and methylome levels. Accordingly, Tfr imprinting stigmata were found on FL-Tfh and FL-B cells, compared to their physiological counterparts. In addition, FL-Tfr co-culture with autologous FL-Tfh or cytotoxic FL-CD8+ T cells inhibited their proliferation in vitro. Finally, although FL-Tfr shared many characteristics with Treg, TCR sequencing analyses demonstrated that part of them derived from precursors shared with FL-Tfh.
UNASSIGNED: Altogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.
UNASSIGNED: The aim of this study was to characterize FL-Tfr phenotype by cytometry, gene expression profile, FL-Tfr origin by transcriptomic analysis, and functionality by in vitro assays.
UNASSIGNED: CD4+CXCR5+CD25hiICOS+ FL-Tfr displayed a regulatory program that is close to classical regulatory T cell (Treg) program, at the transcriptomic and methylome levels. Accordingly, Tfr imprinting stigmata were found on FL-Tfh and FL-B cells, compared to their physiological counterparts. In addition, FL-Tfr co-culture with autologous FL-Tfh or cytotoxic FL-CD8+ T cells inhibited their proliferation in vitro. Finally, although FL-Tfr shared many characteristics with Treg, TCR sequencing analyses demonstrated that part of them derived from precursors shared with FL-Tfh.
UNASSIGNED: Altogether, these findings uncover the role and origin of a Tfr subset in FL niche and may be useful for lymphomagenesis knowledge and therapeutic management.
摘要：
■滤泡性淋巴瘤（FL）是生发中心（GC）B细胞恶性转化的结果。FLB细胞表现出复发性和多样化的遗传改变，他们中的一些人喜欢它们与细胞微环境的直接相互作用，包括滤泡辅助性T细胞(Tfh)。虽然FL-Tfh的关键作用是有据可查的，它们对应的监管机构的影响，滤泡调节性T细胞（Tfr）区室，仍然稀疏。
■本研究的目的是通过细胞计数来表征FL-Tfr表型，基因表达谱，通过转录组学分析的FL-Tfr起源，和功能通过体外测定。
■CD4+CXCR5+CD25hiICOS+FL-Tfr显示出接近经典调节性T细胞（Treg）程序的调节程序，在转录组和甲基化组水平。因此，在FL-Tfh和FL-B细胞上发现了Tfr印迹柱头，与他们的生理对应物相比。此外,FL-Tfr与自体FL-Tfh或细胞毒性FL-CD8T细胞共培养在体外抑制其增殖。最后,尽管FL-Tfr与Treg具有许多共同特征，TCR测序分析表明,它们的一部分源自与FL-Tfh共有的前体。
■总之，这些发现揭示了一个Tfr亚群在FL小生境中的作用和起源,可能对了解淋巴发生和治疗管理有用.
■本研究的目的是通过细胞计数来表征FL-Tfr表型，基因表达谱，通过转录组学分析的FL-Tfr起源，和功能通过体外测定。
■CD4+CXCR5+CD25hiICOS+FL-Tfr显示出接近经典调节性T细胞（Treg）程序的调节程序，在转录组和甲基化组水平。因此，在FL-Tfh和FL-B细胞上发现了Tfr印迹柱头，与他们的生理对应物相比。此外,FL-Tfr与自体FL-Tfh或细胞毒性FL-CD8T细胞共培养在体外抑制其增殖。最后,尽管FL-Tfr与Treg具有许多共同特征，TCR测序分析表明,它们的一部分源自与FL-Tfh共有的前体。
■总之，这些发现揭示了一个Tfr亚群在FL小生境中的作用和起源,可能对了解淋巴发生和治疗管理有用.
