Murphy W J, Keller J R, Harrison C L, Young H A, Longo D L
Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Blood. 1992 Aug 1;80(3):670-7.
Purified natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID) to ascertain their effect on hematopoiesis. When activated and propagated with recombinant human interleukin-2 (rhIL-2) in vitro, SCID spleen cells maintained a phenotypic and lytic spectrum consistent with a pure population of activated NK cells. When added with syngeneic bone marrow cells (BMC) in soft agar, the activated NK cells could support hematopoietic growth in vitro without the addition of exogenous hematopoietic growth factors. However, when syngeneic BMC were added along with cytokines to produce optimal growth conditions, the addition of NK cells was then inhibitory for hematopoietic colony formation. Antibodies to interferon-gamma (IFN-gamma) partially reversed the inhibitory effects. Supernatants from the NK-cell cultures could also exert these effects on hematopoiesis, although to a lesser extent. Analysis of the NK cell RNA demonstrated that activated NK cells express genes for hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and IL-1 beta. The NK cells were also found to express IFN-gamma, transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) mRNA. Analysis of the NK-cell supernatants using factor-dependent myeloid progenitor cell lines showed that the NK cells were producing G-CSF and growth-promoting activity that could not be attributed to IL-1, IL-3, IL-4, IL-5, IL-6, GM-CSF, G-CSF, macrophage CSF (M-CSF), or stem cell factor. The transfer of activated NK cells with BMC into lethally irradiated syngeneic mice resulted in greater BMC engraftment in the recipients. Thus, these results using a pure population of activated NK cells indicate that when activated, these cells can produce a variety of growth factors for hematopoiesis and exert significant hematopoietic growth-promoting effects in vivo.
从严重联合免疫缺陷（SCID）小鼠中获取纯化的自然杀伤（NK）细胞，以确定它们对造血作用的影响。当在体外与重组人白细胞介素-2（rhIL-2）一起激活并增殖时，SCID脾细胞维持与纯激活NK细胞群体一致的表型和裂解谱。当在软琼脂中加入同基因骨髓细胞（BMC）时，激活的NK细胞在不添加外源性造血生长因子的情况下能够支持体外造血生长。然而，当同基因BMC与细胞因子一起添加以产生最佳生长条件时，NK细胞的添加随后对造血集落形成具有抑制作用。抗干扰素-γ（IFN-γ）抗体部分逆转了这种抑制作用。NK细胞培养物的上清液也能对造血作用产生这些影响，尽管程度较小。对NK细胞RNA的分析表明，激活的NK细胞表达造血生长因子的基因，如粒细胞-巨噬细胞集落刺激因子（GM-CSF）、粒细胞集落刺激因子（G-CSF）和白细胞介素-1β（IL-1β）。还发现NK细胞表达IFN-γ、转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α（TNF-α）mRNA。使用依赖因子的髓系祖细胞系对NK细胞上清液进行分析表明，NK细胞产生的G-CSF和生长促进活性不能归因于IL-1、IL-3、IL-4、IL-5、IL-6、GM-CSF、G-CSF、巨噬细胞集落刺激因子（M-CSF）或干细胞因子。将激活的NK细胞与BMC转移到经致死性照射的同基因小鼠中，导致受体中BMC的植入增加。因此，使用纯激活NK细胞群体的这些结果表明，激活后，这些细胞可以产生多种造血生长因子，并在体内发挥显著的造血生长促进作用。
