Department of Medicine, Division of Rheumatology, Philadelphia VA Medical Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Laboratory of Systems Immunology, Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX 78712, USA.
Cell Rep. 2019 Sep 17;28(12):3047-3060.e7. doi: 10.1016/j.celrep.2019.08.037.
CXCR5 is a key marker of follicular helper T (T) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified a population of CXCR5 CD4 T cells with T-cell-like features. This CXCR5 subset becomes expanded in severe HIV infection and is characterized by the upregulation of activation markers and high PD-1 and ICOS surface expression. Integrated analyses on the phenotypic heterogeneity, functional capacity, T cell receptor (TCR) repertoire, transcriptional profile, and epigenetic state of CXCR5PD-1ICOS T cells revealed a shared clonal relationship with T cells. CXCR5PD-1ICOS T cells retained a poised state for CXCR5 expression and exhibited a migratory transcriptional program. TCR sequence overlap revealed a contribution of LN-derived CXCR5PD-1ICOS T cells to circulating CXCR5 CD4 T cells with B cell help function. These data link LN pathology to circulating T cells and expand the current understanding on the diversity of T cells that regulate B cell responses during chronic inflammation.
CXCR5 是滤泡辅助 T（T）细胞的一个关键标志物。我们使用感染 HIV 的患者的初级淋巴结（LNs），鉴定出一群具有 T 细胞样特征的 CXCR5 CD4 T 细胞。该 CXCR5 亚群在严重的 HIV 感染中扩增，并表现出激活标志物的上调和高 PD-1 和 ICOS 表面表达。对 CXCR5 PD-1 ICOS T 细胞的表型异质性、功能能力、T 细胞受体（TCR）库、转录谱和表观遗传状态进行综合分析，揭示了与 T 细胞的共享克隆关系。CXCR5 PD-1 ICOS T 细胞保留了 CXCR5 表达的启动状态，并表现出迁移性转录程序。TCR 序列重叠表明 LN 来源的 CXCR5 PD-1 ICOS T 细胞有助于循环中具有 B 细胞辅助功能的 CXCR5 CD4 T 细胞。这些数据将 LN 病理学与循环 T 细胞联系起来，并扩展了目前对慢性炎症期间调节 B 细胞反应的 T 细胞多样性的理解。
