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

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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.