Eliopoulos G D, Coulocheri S A, Eliopoulos A G, Katrinakis G, Karkavitsas N, Kyriakou D, Vaiopoulos G, Foudoulakis A
Department of Haematology University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Eur J Haematol. 1992 May;48(5):237-43. doi: 10.1111/j.1600-0609.1992.tb01800.x.
Natural killer (NK) cells were analyzed in 38 untreated patients with refractory anaemia with excess of blasts (RAEB), using cytotoxicity assays and immunofluorescence with monoclonal antibodies. We found that patients with RAEB have normal numbers of peripheral blood and bone marrow NK cells. NK cells from RAEB patients express very low natural-killer cell activity (NKa) which may be increased significantly with recombinant alpha-interferon and recombinant interleukin-2, although it remains below the lower limit of the control range. The cells exhibit normal tumour cell binding capacity, but fail to release sufficient amounts of natural-killer cytotoxic factors (NKCFs) upon their interaction with NK-sensitive K562 cell targets or their stimulation with phytohaemagglutinin. Our results suggest that defective NKa in RAEB patients may be due, at least in part, to impaired release of functionally active NKCFs. This disturbance is probably the result of some intrinsic defect of RAEB NK cells in NKCF production, storage, and/or release. The possibility of an impairment in the activation signal provided by the stimulatory K562 cells cannot be excluded, although it seems unlikely. We postulate that this abnormality might represent a manifestation of dysplastic haemopoiesis. Further studies are certainly needed to investigate whether other defective mechanisms are also implicated in the determination of the low NKa in patients with RAEB.
采用细胞毒性试验和单克隆抗体免疫荧光法，对38例未经治疗的伴有原始细胞增多的难治性贫血（RAEB）患者的自然杀伤（NK）细胞进行了分析。我们发现，RAEB患者外周血和骨髓中的NK细胞数量正常。RAEB患者的NK细胞表达的自然杀伤细胞活性（NKa）非常低，尽管其仍低于对照范围的下限，但重组α干扰素和重组白细胞介素-2可使其显著升高。这些细胞表现出正常的肿瘤细胞结合能力，但在与NK敏感的K562细胞靶点相互作用或用植物血凝素刺激时，未能释放足够量的自然杀伤细胞毒性因子（NKCFs）。我们的结果表明，RAEB患者的NKa缺陷可能至少部分归因于功能活性NKCFs释放受损。这种紊乱可能是RAEB NK细胞在NKCF产生、储存和/或释放方面某些内在缺陷的结果。尽管似乎不太可能，但也不能排除刺激K562细胞提供的激活信号受损的可能性。我们推测这种异常可能代表了造血异常的一种表现。当然需要进一步研究来调查其他缺陷机制是否也与RAEB患者低NKa的确定有关。
