澳大利亚彼得·多尔蒂感染与免疫研究所Ashraful Haque研究团队在研究中取得进展。他们利用疟疾感染期间CD4⁺ T细胞的动态转录组学揭示了CD4⁺ T细胞内效应因子转变为记忆因子。该研究于2020年10月12日发表于国际学术期刊《自然-免疫学》。

研究人员利用单细胞RNA测序和计算模型来追踪疟原虫感染和治疗过程中CD4⁺  T细胞的记忆发育。在没有中央记忆的前提下，两条发育为辅助性T细胞 1（TH1）和滤泡辅助性T细胞（TFH）的转录程序在三个星期内发生收缩并部分合并。单个克隆产生的子细胞占据了TH1和TFH的发育轨迹，而命运映射则表明这些谱系具有最低可塑性。

研究人员揭示了TFH和中枢记忆之间的关系，抗疟药调节了这些反应并增强了TH1的记忆。最后，单细胞表观基因组学证实效应子之间的异质性被部分重置。因此，在疟疾感染期间，CD4⁺  T细胞中的效应因子逐渐过渡为记忆因子，并受抗寄生虫药物的调节。该研究提供了用于检查动态基因表达以及基因与基因相关性的新方法。

据介绍，目前仍缺乏在基因组规模上对CD4⁺  T细胞记忆形成动力学的研究。在疟疾流行地区，抗疟疾化学疗法在停用后仍能提供长期保护，这与对CD4⁺ T细胞的影响有关。

附：英文原文

Title: Transcriptome dynamics of CD4 + T cells during malaria maps gradual transit from effector to memory

Author: Megan S. F. Soon, Hyun Jae Lee, Jessica A. Engel, Jasmin Straube, Bryce S. Thomas, Clara P. S. Pernold, Lachlan S. Clarke, Pawat Laohamonthonkul, Rohit N. Haldar, Cameron G. Williams, Lianne I. M. Lansink, Marcela L. Moreira, Michael Bramhall, Lambros T. Koufariotis, Scott Wood, Xi Chen, Kylie R. James, Tapio Lnnberg, Steven W. Lane, Gabrielle T. Belz, Christian R. Engwerda, David S. Khoury, Miles P. Davenport, Valentine Svensson, Sarah A. Teichmann, Ashraful Haque

Issue&Volume: 2020-10-12

Abstract: The dynamics of CD4+ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4+ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (TH1) and follicular helper T (TFH) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated TH1 and TFH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between TFH and central memory were revealed, with antimalarials modulating these responses and boosting TH1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4+ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene–gene correlations.

DOI: 10.1038/s41590-020-0800-8

Source: https://www.nature.com/articles/s41590-020-0800-8