Single-cell RNAseq of HA-specific CD8 T cells isolated from the hypothalamus and the spleen of mice expressing the model antigen HA in orexinergic neurons. Single-cell RNAseq of HA-specific CD8 T cells isolated from the hypothalamus and the spleen of mice expressing the model antigen HA in orexinergic neurons

We previously generated the Orex-HA mouse model in which orexin-producing neurons residing in the hypothalamus selectively expressed a model self-antigen, namely hemagglutinin (HA) from the H1N1 influenza virus. In this model the adoptive transfer of in vitro activated HA-specific CD8 T cells leads to the specific loss of orexinergic neurons located in the hypothalamus. To assess the phenotype and investigate the pathogenic mechanisms and the potential tissue-resident properties of autoreactive (HA-specific) CD8 T cells infiltrating the hypothalamus of Orex-HA mice , we performed a single-cell transcriptomic analysis (scRNA-seq) of HA-specific CD8+ T cells isolated from the hypothalamus and the spleen at day 30 after T cell transfer in Orex-HA mice.

本研究团队此前构建了Orex-HA小鼠模型，该模型中位于下丘脑的产食欲素神经元可选择性表达模式自身抗原——H1N1流感病毒的血凝素（hemagglutinin, HA）。在此模型中，过继转移（adoptive transfer）体外（in vitro）活化的HA特异性CD8 T细胞，可导致下丘脑内食欲素能神经元的特异性丢失。为了评估浸润Orex-HA小鼠下丘脑的自身反应性（autoreactive）HA特异性CD8阳性T细胞的表型，探究其致病机制与潜在的组织驻留特性，研究人员在T细胞移植后第30天，从Orex-HA小鼠的下丘脑与脾脏中分离HA特异性CD8阳性T细胞，并对其开展了单细胞转录组分析（single-cell transcriptomic analysis, scRNA-seq）。