Saikawa Y, Hasui M, Miura M, Tachinami T, Katayama K, Takano N, Miyawaki T, Koizumi S, Taniguchi N
Department of Pediatrics, School of Medicine, Kanazawa University, Ishikawa, Japan.
Cell Immunol. 1989 Nov;124(1):38-49. doi: 10.1016/0008-8749(89)90110-x.
Human recombinant interleukin 2 (IL 2) and highly purified murine interleukin 3 (IL 3) were tested for their ability to generate NK activity in bone marrow cells from mice with severe combined immunodeficiency. IL 2 alone could dose dependently induce NK activity in marrow cells as determined by cytotoxicity against YAC-1 target cells. It was demonstrated that IL 3 had dual effects on the generation of NK activity in this culture system. The addition of IL 3 resulted in inhibition of NK cell activity seen at high concentrations of IL 2. In contrast, when IL 3 was added together with low concentrations of IL 2, the generation of NK cells as judged by cytotoxicity assay as well as the appearance of cells with NK phenotypes was markedly augmented. In some experiments, mice were treated with 5-fluorouracil (5-FU) to eliminate relatively differentiated NK precursors from bone marrow cells. It was noted that the residual immature marrow cells from 5-FU-treated mice showed little NK activity even after the culture with high concentrations of IL 2. Importantly, IL 3 could induce the generation of NK activity from 5-FU-treated marrow cells in the presence of IL 2. Kinetic studies indicated that NK activity was appreciably generated from 5-FU-treated marrow cells when preincubated with IL 3 at least for 12 hr and subsequently cultured with IL 2. The cells bearing IL 2 receptors appeared in 5-FU-treated marrow cells, even though cultured only with IL 3, which implied that IL 3 could support the development of very primitive NK cells from IL 2-unresponsive to IL 2-responsive states. These results suggested that IL 3 might play a crucial role for the IL 2-induced generation of NK cells in bone marrow through promoting the expression of IL 2R on NK progenitor cells.
对人重组白细胞介素2（IL-2）和高度纯化的小鼠白细胞介素3（IL-3）在严重联合免疫缺陷小鼠的骨髓细胞中产生自然杀伤（NK）活性的能力进行了检测。单独使用IL-2可剂量依赖性地诱导骨髓细胞中的NK活性，这通过对YAC-1靶细胞的细胞毒性来确定。结果表明，IL-3对该培养系统中NK活性的产生具有双重作用。添加IL-3会导致在高浓度IL-2时出现NK细胞活性的抑制。相反，当IL-3与低浓度IL-2一起添加时，通过细胞毒性试验判断的NK细胞生成以及具有NK表型的细胞出现均明显增加。在一些实验中，用5-氟尿嘧啶（5-FU）处理小鼠以从骨髓细胞中消除相对分化的NK前体细胞。值得注意的是，即使在用高浓度IL-2培养后，来自5-FU处理小鼠的残留未成熟骨髓细胞也显示出很少的NK活性。重要的是，在存在IL-2的情况下，IL-3可诱导5-FU处理的骨髓细胞产生NK活性。动力学研究表明，当与IL-3预孵育至少12小时并随后用IL-2培养时，5-FU处理的骨髓细胞可明显产生NK活性。即使仅用IL-3培养，5-FU处理的骨髓细胞中也出现了携带IL-2受体的细胞，这意味着IL-3可以支持非常原始的NK细胞从对IL-2无反应状态发展为对IL-2有反应状态。这些结果表明，IL-3可能通过促进NK祖细胞上IL-2受体的表达，在骨髓中IL-2诱导的NK细胞生成中发挥关键作用。
