Development of thymic NK cells from double negative 1 thymocyte precursors
Development of thymic NK cells from double negative 1 thymocyte precursors
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DOI：
10.1182/blood-2011-06-359679
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发表时间：
2011-09-29
期刊：
影响因子：
20.3
通讯作者：
Yokoyama, Wayne M.
中科院分区：
文献类型：
--
作者：
Vargas, Claudia L.;Poursine-Laurent, Jennifer;Yokoyama, Wayne M.
自然杀伤细胞（NK）和NK细胞亚群的分化需要一个完整的胸腺，即胸腺NK细胞，目前尚不清楚。先前的体外研究表明，双阴性(CD4（-)CD8(-)， DN）胸腺细胞可以发育成具有NK细胞标记的细胞，但这些细胞尚未得到很好的表征。在此，我们生成并表征了从胸腺DN前体分化的NK细胞。从Rag1（-/-）小鼠中分离出的DN1 (CD44(+)CD25(-) CD122(-)NK1.1（-）胸腺细胞过继转入Rag1(-/-)Ly5.1基因小鼠。胸腺内注射后，发现供体来源的细胞表型类似胸腺NK细胞。为了进一步研究它们的分化，我们将经过筛选的DN1 CD122(-)NK1.1（-）胸腺细胞植入经IL-15、IL-7、Flt3L和干细胞因子照射的OP9骨髓基质细胞上。7 d后出现NK1.1（+）细胞。体外分化的NK细胞获得了与未成熟骨髓来源的NK细胞相关的标记，但也表达CD127，这通常在胸腺NK细胞上发现。此外，我们发现胸腺前体产生的体外细胞在受到刺激时分泌细胞因子，并在靶暴露时脱颗粒。总之，这些数据表明功能性胸腺NK细胞可以从DN1祖细胞群发育而来。(血。2011;118 (13):3570 - 3578)
The differentiation of natural killer (NK) cells and a subpopulation of NK cells which requires an intact thymus, that is, thymic NK cells, is poorly understood. Previous in vitro studies indicate that double negative (CD4(-)CD8(-), DN) thymocytes can develop into cells with NK cell markers, but these cells have not been well characterized. Herein, we generated and characterized NK cells differentiating from thymic DN precursors. Sorted DN1 (CD44(+)CD25(-)) CD122(-)NK1.1(-) thymocytes from Rag1(-/-) mice were adoptively transferred into Rag1(-/-)Ly5.1 congenic mice. After intrathymic injection, donor-derived cells phenotypically resembling thymic NK cells were found. To further study their differentiation, we seeded sorted DN1 CD122(-)NK1.1(-) thymocytes on irradiated OP9 bone marrow stromal cells with IL-15, IL-7, Flt3L, and stem cell factor. NK1.1(+) cells emerged after 7 days. In vitro differentiated NK cells acquired markers associated with immature bone marrow-derived NK cells, but also expressed CD127, which is typically found on thymic NK cells. Furthermore, we found that in vitro cells generated from thymic precursors secreted cytokines when stimulated and degranulated on target exposure. Together, these data indicate that functional thymic NK cells can develop from a DN1 progenitor cell population. (Blood. 2011;118(13):3570-3578)