| 研究実績の概要 |
Although it is widely believed that invariant Vα14 NKT cells are generated from CD4+CD8+ double-positive thymocytes by selection on CD1d, a process termed the DP pathway, it is still not fully understood whether NKT cells develop exclusively by the DP pathway in a manner closely resembling that of conventional αβ T cells, or some alternatives to this pathway exist. Here we provide genetic evidence supporting the presence of an alternative developmental pathway of NKT cells from late CD4-CD8- double-negative stage thymocytes without passing DP pathway, where the DP-specific ablation of Rag2 resulted in a loss of Vα14Jα18 rearrangement by DP cells suggesting mature NKT cells developed in this mouse were generated from DN thymocytes with intact expressions of both Rag2 and Vα14Jα18 transcripts. Moreover, fate-mapping approach by introducing DP-specific E8III-Cre transgene into Rosa26YFP reporter mice, where a reporter gene expression labels progenies of DP precursors, allowed detecting NKT cells without expression of YFP reporter demonstrating these cells were differentiated through the DN pathway without passing the DP stage. Furthermore, NKT cells generated by DN pathway show characteristics of Th1-biased cytotoxic effector cells suggesting this developmental pathway gives rise preferentially to Th1-type NKT cells. Our present findings provide new insights in understanding the development of NKT cells in the thymus, which seems to be different from that of conventional αβ T cells.
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