Elucidation of Natural Killer T cell development in a mice model of rheumatoid arthritis

我们重新分析了单细胞转录组数据，并将胸腺中的NKT细胞分为几类，包括CD4+CD8+双阳性祖细胞、增殖细胞以及NKT1、NKT2和NKT17细胞。对推测的谱系的分析表明，NKT亚群表型已经存在于增殖细胞中，并且是在DP-GT；增殖阶段确定的。一组促凋亡细胞具有与NKT亚群匹配的特征，并显示出激活标志的表达增加，这表明过度激活标志着它们的缺失(负选择)。大多数细胞都有一个典型的受体，其阿尔法链由TRAV11和TRAJ18基因组成。有一小部分细胞具有非规范受体。虽然这可能代表污染细胞，但在分化的NKT细胞中也存在非规范受体。根据我们对其他数据集的经验，像发育中的T细胞这样的污染细胞将显示为一个不同的簇。携带非典型性TCR的NKT可代表携带更多样化TCR的2型NKT。

We have reanalyzed the single cell transcriptome data and classify NKT cells in the thymus into several populations including CD4+CD8+ double positive progenitor cells, proliferating cells and NKT1, NKT2 and NKT17 cells. Analysis of the inferred lineage suggests NKT subpopulation phenotype already exists in proliferating cells and is determined during the DP->Proliferating step. A group of pro-apoptotic cells have signatures matching the NKT subpopulations and show increased expression of markers of activation suggesting that overactivation marked them for deletion (negative selection). Most of the cells have a canonical receptor with alpha chain made of TRAV11 and TRAJ18 genes. A fraction of the cells have non-canonical receptors. Although this could represent contaminating cells, non-canonical receptors exist also in differentiated NKT cells. Contaminating cells like developing T cells would show as a distinct clusters, based on our experience with other datasets. NKTs harboring a non-canonical TCR could represent type 2 NKTs, which carry a more diverse TCR.