Turnover and proliferation of NK cells in steady state and lymphopenic conditions
Turnover and proliferation of NK cells in steady state and lymphopenic conditions
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DOI：
10.4049/jimmunol.172.2.864
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Raulet, DH
中科院分区：
文献类型：
--
作者：
Jamieson, AM;Isnard, P;Raulet, DH
为了深入了解NK细胞动力学，我们研究了NK细胞在正常和淋巴细胞减少条件下的周转和增殖率。与先前报道NK细胞的快速更新不同，连续的5-溴-2'-脱氧尿苷（BrdU）标记研究表明，在成熟小鼠中标记50%的脾脏NK细胞所需的时间为17天，与记忆T细胞的标记率相似。相比之下，在年轻小鼠中，脾脏NK细胞被BrdU快速标记，尽管细胞周期分析和BrdU脉冲标记研究表明，这种增殖大部分发生在前体群体中。骨髓NK细胞循环的比例略高，表明这些增殖细胞是大部分不分裂或缓慢分裂的脾NK细胞的前体。成熟小鼠脾NK细胞在转移到正常小鼠身上时也没有明显增殖，但在转移到辐照小鼠身上时却有增殖。因此，NK细胞和T细胞一样，在淋巴细胞减少的环境中进行稳态增殖。NK细胞的稳态增殖不依赖于宿主细胞I类分子或宿主产生IL-15。然而，在IL-15（-/-）宿主中，恢复的NK细胞数量要低得多。这些结果表明，IL-15对NK细胞的稳态增殖不是必需的，但对NK细胞的存活是必需的。我们的结果为NK细胞的产生和替代提供了重要的基础信息。中华免疫学杂志，2004,17(2):864-870。
To gain insight into NK cell dynamics, we investigated the turnover and proliferation rates of NK cells in normal and lymphopenic conditions. In contrast to previous reports suggesting a very rapid turnover of NK cells, continuous 5-bromo-2'-deoxyuridine (BrdU)-labeling studies demonstrated that the time necessary for labeling 50% of splenic NK cells in mature mice was 17 days, similar to the rate of labeling of memory T cells. In contrast, in young mice, splenic NK cells labeled very rapidly with BrdU, although cell cycle analyses and BrdU pulse-labeling studies suggested that most of this proliferation occurred in a precursor population. A somewhat larger percentage of bone marrow NK cells was cycling, suggesting that these proliferating cells are the precursors of the mostly nondividing or slowly dividing splenic NK cells. Splenic NK cells from mature mice also did not proliferate significantly when transferred to normal mice, but did proliferate when transferred to irradiated mice. Thus, NK cells, like T cells, undergo homeostatic proliferation in a lymphopenic environment. Homeostatic proliferation of NK cells was not dependent on host cell class I molecules or host production of IL-15. Nevertheless, the number of recovered NK cells was much lower in IL-15(-/-) hosts. These results suggest that IL-15 is not essential for homeostatic proliferation of NK cells, but is necessary for survival of the NK cells. Our results provide important basic information concerning the production and replacement of NK cells. The Journal of Immunology, 2004, 172: 864-870.