Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan.
J Immunol. 2011 Nov 15;187(10):5162-9. doi: 10.4049/jimmunol.1101561. Epub 2011 Oct 3.
In mice lacking IL-15, NK cell development is arrested at immature stages, providing an opportunity to investigate the earliest developing NK cells that would respond to IL-15. We show in this study that immature NK cells were present in the spleen as well as bone marrow (BM) and contained IL-15-high-responder cells. Thus, mature NK cells were generated more efficiently from IL-15(-/-) than from control donor cells in radiation BM chimeras, and the rate of IL-15-induced cell division in vitro was higher in NK cells in the spleen and BM from IL-15(-/-) mice than in those from wild-type mice. Phenotypically, NK cells developed in IL-15(-/-) mice up to the minor but discrete CD11b(-)CD27(+)DX5(hi)CD51(dull)CD127(dull)CD122(hi) stage, which contained the majority of Ly49G2(+) and D(+) NK cells both in the spleen and BM. Even among wild-type splenic NK cells, IL-15-induced proliferation was most prominent in CD11b(-)DX5(hi) cells. Notably, IL-15-mediated preferential expansion (but not conversion from Ly49(-) cells) of Ly49(+) NK cells was observed in vitro only for NK cells in the spleen. These observations indicated the uneven distribution of NK cells of different developing stages with variable IL-15 responsiveness in these lymphoid organs. Immature NK cells in the spleen may contribute, as auxiliaries to those in BM, to the mature NK cell compartment through IL-15-driven extramarrow expansion under steady-state or inflammatory conditions.
在缺乏白细胞介素 15（IL-15）的小鼠中，NK 细胞的发育停滞在不成熟阶段，这为研究对 IL-15 有反应的最早发育的 NK 细胞提供了机会。在本研究中，我们发现不成熟的 NK 细胞存在于脾脏和骨髓（BM）中，并含有高反应性的 IL-15 细胞。因此，在辐射 BM 嵌合体中，来自 IL-15（-/-）的成熟 NK 细胞比来自对照供体细胞更有效地生成，并且 IL-15 诱导的体外细胞分裂率在来自 IL-15（-/-）小鼠的脾脏和 BM 的 NK 细胞中高于来自野生型小鼠的 NK 细胞。表型上，IL-15（-/-）小鼠中 NK 细胞的发育达到了一个较小但明显的 CD11b（-）CD27（+）DX5（hi）CD51（dull）CD127（dull）CD122（hi）阶段，该阶段包含了脾脏和 BM 中大多数 Ly49G2（+）和 D（+）NK 细胞。即使在野生型脾脏 NK 细胞中，IL-15 诱导的增殖在 CD11b（-）DX5（hi）细胞中最为明显。值得注意的是，仅在脾脏 NK 细胞中观察到 IL-15 介导的 Ly49（+）NK 细胞的优先扩增（而不是从 Ly49（-）细胞转化）。这些观察结果表明，在这些淋巴器官中，不同发育阶段的 NK 细胞具有不同的 IL-15 反应性，其分布不均匀。脾脏中的不成熟 NK 细胞可能作为 BM 中的 NK 细胞的辅助细胞，通过 IL-15 驱动的骨髓外扩增，在稳态或炎症条件下有助于成熟 NK 细胞的形成。
