Malignant clonal expansion of an NK cell subpopulation andits suppressive effect on the growth of hemopoietic stem cells.

自然杀伤(NK)细胞在形态上与大颗粒淋巴细胞(LGL)难以区分，被认为在造血调控中起着重要作用。从一名14岁女孩身上分离出克隆性白血病NK细胞群。它们具有Leu-11^、Leu-7^-表型。由于NK细胞活性较低，但在重组人白介素2(rIL-2)刺激下可显著增强，而干扰素-(干扰素-γ)却不能刺激，这一NK细胞亚群似乎属于NK细胞成熟的早熟阶段。由于在整个临床过程中存在严重的中性粒细胞减少，我们研究了这一NK亚群对粒细胞-巨噬细胞集落形成细胞(GM-CDC)体外生长的影响。当在rIL-2存在的情况下将这个NK亚群加入到使用正常骨髓细胞的GM-CFC检测系统中时，显示出显著的GM-CFCs抑制。由rIL-2刺激的NK细胞的培养上清液也显示出显著的抑制活性，该细胞具有高水平的干扰素-γ。用干扰素-γ特异性抗体处理培养上清液，可消除对GM-CFCs的抑制作用。这些数据表明，在rIL-2存在的情况下，这一独特的早熟NK细胞亚群产生了干扰素-γ，它似乎参与了对造血祖细胞的抑制。

Natural killer (NK) cells, morphologically indistinguishable from large granular lymphocytes (LGLs), are thought to have an important role in the regulation of hematopoiesis. A clonal leukemic population of NK cells was isolated from a 14-year-old girl. They had a Leu-11^+, Leu-7^- phenotype. Since the NK activity was low but was remarkably augmented by stimulation with recombinant human interleukin 2 (rIL-2), but not interferon- (IFN-<gamma>), this NK subset seems to belong to a premature stage in the maturation of NK cells. Because of severe neutropenia throughout the clinical course, we investigated the effects of this NK subpopulation on the in vitro growth of granulocyte-macrophage colony forming cells (GM-CDC). When this NK subset in the presence of rIL-2 was added to the GM-CFC assay system employing normal bone marrow cells, a remarkable suppression of GM-CFC was demonstrated. Culture supernatants from the rIL-2-stimulated NK cells, which had a high level of IFN-<gamma>, also exhibited a significant suppressive activity. Treatment of the supernatants with a specific antibody against IFN-<gamma> abrogated the inhibitory effect on GM-CFC. These data indicate that this unique subset of premature NK cells in the presence of rIL-2 produceIFN-<gamma> which seems to be involved in the suppression of myelopoietic progenitor cells.