小柯机器人

美国耶鲁大学医学院Ya-Chi Ho团队利用单细胞多组学揭示HIV-1在扩增的细胞毒性T细胞克隆中的持久性。相关论文于2022年3月22日在线发表在《免疫》杂志上。

研究人员使用了单细胞ECCITE-seq，它在同一单细胞内捕获表面蛋白表达、细胞转录组、HIV-1 RNA和TCR序列，来追踪了6个HIV-1感染者（病毒感染期间和抑制性抗逆转录病毒治疗后）和2个未感染者的纵向存档样本的克隆扩增动态，这些样本是在未刺激条件下和CMV和HIV-1抗原刺激后。尽管进行了抗逆转录病毒治疗，持续的抗原和TNF反应形成了T细胞的克隆扩增。HIV-1驻留在Th1极化、抗原反应的T细胞中，表达BCL2和SERPINB9，可能抵抗细胞死亡。HIV-1 RNA⁺的T细胞克隆大小较大，在病毒感染期间建立，在病毒抑制后持续存在，并富含GZMB⁺细胞毒性效应记忆Th1细胞。靶向HIV-1感染的细胞毒性CD4⁺ T细胞和克隆扩增的驱动因素为HIV-1的根除提供了另一个方向。

据介绍，了解HIV-1感染的CD4⁺ T细胞克隆性扩增的驱动因素和标志物对HIV-1的根除至关重要。

附：英文原文

Title: Single-cell multiomics reveals persistence of HIV-1 in expanded cytotoxic T cell clones

Author: Jack A. Collora, Runxia Liu, Delia Pinto-Santini, Neal Ravindra, Carmela Ganoza, Javier R. Lama, Ricardo Alfaro, Jennifer Chiarella, Serena Spudich, Karam Mounzer, Pablo Tebas, Luis J. Montaner, David van Dijk, Ann Duerr, Ya-Chi Ho

Issue&Volume: 2022-03-22

Abstract: Understanding the drivers and markers of clonally expanding HIV-1-infected CD4+ T cells is essential for HIV-1 eradication. We used single-cell ECCITE-seq, whichcaptures surface protein expression, cellular transcriptome, HIV-1 RNA, and TCR sequenceswithin the same single cell to track clonal expansion dynamics in longitudinally archivedsamples from six HIV-1-infected individuals (during viremia and after suppressiveantiretroviral therapy) and two uninfected individuals, in unstimulated conditionsand after CMV and HIV-1 antigen stimulation. Despite antiretroviral therapy, persistentantigen and TNF responses shaped T cell clonal expansion. HIV-1 resided in Th1-polarized,antigen-responding T cells expressing BCL2 and SERPINB9 that may resist cell death. HIV-1 RNA+ T cell clones were larger in clone size, established during viremia, persistent afterviral suppression, and enriched in GZMB+ cytotoxic effector memory Th1 cells. Targeting HIV-1-infected cytotoxic CD4+ T cells and drivers of clonal expansion provides another direction for HIV-1 eradication.

DOI: 10.1016/j.immuni.2022.03.004

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00127-3

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