Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.
Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor.
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DOI：
10.1084/jem.180.4.1395
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发表时间：
1994-10-01
期刊：
影响因子：
--
通讯作者：
Caligiuri MA
中科院分区：
文献类型：
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作者：
Carson WE;Giri JG;Lindemann MJ;Linett ML;Ahdieh M;Paxton R;Anderson D;Eisenmann J;Grabstein K;Caligiuri MA
白细胞介素15（IL-15）是一种新的细胞因子，最近被克隆和表达。尽管它与IL-2没有序列同源性，但IL- 15与IL-2受体（IL-2 R）的组分相互作用。在本研究中，我们进行了重组IL-15的表型和功能不同的高度纯化的人自然杀伤（NK）细胞群体的功能分析。人NK细胞的CD 56 bright亚群组成型表达高亲和力IL-2 R，并在皮摩尔量的IL-2结合后表现出活跃的增殖反应。使用增殖测定，IL-15显示出与IL-2的剂量-反应曲线不同的非常陡峭的剂量-反应曲线。IL-15的增殖作用可被抗IL-2 R β（p75）消除，但不能被抗IL-2 R α（p55）消除。两种抗体均能抑制IL-2对CD 56 bright NK细胞的增殖作用。CD 56 dim NK细胞在不存在高亲和力IL-2 R的情况下表达中等亲和力IL-2 R。通过增强的NK细胞毒性活性、抗体依赖性细胞毒性和NK细胞产生干扰素γ、肿瘤坏死因子α和粒细胞/巨噬细胞集落刺激因子来测量，IL-15对CD 56 dim NK细胞的激活与IL-2的激活相似。IL-15增强的NK细胞毒活性可被抗IL-2 R β单克隆抗体完全阻断。在存在抗IL-2 R β的情况下，放射性标记的IL-2和IL-15与CD 56 dim NK细胞的结合受到抑制。放射性标记的IL-15和IL-2与NK富集的人淋巴细胞结合的Scatchard分析揭示了两种配体的高亲和力和中等亲和力受体的存在。IL-15是通过IL-2 R的组分以与IL-2相似但不相同的模式激活人NK细胞的配体。与IL-2不同，IL-15由活化的单核细胞/巨噬细胞产生。IL-15的发现可能增加我们对单核细胞/巨噬细胞如何参与NK细胞功能调节的理解。
Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL- 15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK- enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.