PDF(Pubmed)
Abstract：
Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4+ T cell subsets remain unresolved. Here, we examine antigen-experienced CD4+ T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic TEM cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with TCM/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4+ T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4+ T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.
摘要：
疟疾流行地区的儿童可以在短时间内反复感染疟原虫。再感染对多个共存的CD4+T细胞亚群的影响仍未解决。这里,我们检查了在小鼠再感染过程中经历抗原的CD4+T细胞，使用scRNA-seq/TCR-seq和空间转录组学。TCR转基因TEM细胞在增殖之前启动快速的Th1/Tr1回忆反应，虽然GCTfh同行是耐火的，TCM/Tfh样细胞表现出适度的非增殖反应。Th1召回是主要Th1响应的部分传真，没有上调的效应子相关基因是唯一的回忆。多克隆,TCR多样化，CD4+T细胞表现出相似的回忆动态，单个克隆产生多种效应物，包括高度增殖的Th1/Tr1细胞，以及缺乏增殖能力的GCTfh和Tfh样细胞。因此，我们显示了由脾脏中多个共存的CD4+T细胞亚群安装的回忆反应的实质性多样性，并提供图形用户界面，用于研究再感染期间的基因表达动力学和克隆关系。
