Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage
Alternative pathway for the development of Vα14+ NKT cells directly from CD4-CD8- thymocytes that bypasses the CD4+CD8+ stage
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DOI：
10.1038/ni.3668
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发表时间：
2017-03-01
影响因子：
30.5
通讯作者：
Taniguchi, Masaru
中科院分区：
文献类型：
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作者：
Dashtsoodol, Nyambayar;Shigeura, Tomokuni;Taniguchi, Masaru
虽然不变性V(α)14(+)-自然杀伤T细胞（NKT细胞）被认为是由CD4(+)CD8（+）双阳性（DP）胸腺细胞产生的，但CD4(-)CD8（-）双阴性（DN） NKT细胞的发育起源仍未解决。在这里，我们提供了明确的遗传证据，通过对DP阶段特异性缺失重组酶成分Rag2 （Rag2）基因表达的小鼠研究和命运定位方法，支持存在另一种发育途径的建议，通过该途径，部分具有强T-辅助型-1 （T(H)1）偏向和细胞毒性特征的DN NKT细胞从DN晚期胸腺细胞发展而来，绕过DP阶段。这些发现为理解NKT细胞的发育提供了新的见解，并提出了不变T细胞抗原受体表达时间的作用。确定NKT细胞的功能特性。
Although invariant V(alpha)14(+)-natural killer T cells (NKT cells) are thought to be generated from CD4(+)CD8(+) double-positive (DP) thymocytes, the developmental origin of CD4(-)CD8(-) double-negative (DN) NKT cells still remains unresolved. Here we provide definitive genetic evidence obtained, through studies of mice with DP-stage-specific ablation of expression of the gene encoding the recombinase component RAG-2 (Rag2) and by a fate-mapping approach, that supports the proposal of the existence of an alternative developmental pathway through which a fraction of DN NKT cells with strong T-helper-type-1 (T(H)1)-biased and cytotoxic characteristics develop from late DN-stage thymocytes, bypassing the DP stage. These findings provide new insight into understanding of the development of NKT cells and propose a role for timing of expression of the invariant T cell antigen receptor. in determining the functional properties of NKT cells.