期刊
NATURE IMMUNOLOGY
卷 18, 期 3, 页码 274-282出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3668
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资金
- Japan Society for the Promotion of Science (KAKENHI) [24790490, 23229005]
- Grants-in-Aid for Scientific Research [24790490, 15K08291, 23229005] Funding Source: KAKEN
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.
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