Eliopoulos G D, Vaiopoulos G, Kyriakou D, Eliopoulos A G, Papadaki H, Katrinakis G, Alexandrakis M
Department of Hematology of the University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Haematologica. 1993 Jul-Aug;78(4):219-24.
Chronic LGL-proliferative disease (LGL-PD) is a clonal expansion of cells with large granular lymphocyte (LGL) morphology. In most cases, proliferating cells express both suppressor/cytolytic T-cell and natural killer (NK) cell surface markers, but other cell phenotypes may be observed. LGL-PD lymphocytes have been found to lack or show very low natural killer cell activity (NKa). The aim of the present paper is to investigate the underlying mechanisms responsible for impaired NKa in a homogeneous group of five selected LGL-PD patients with a CD3+, CD8+, CD57+ cell phenotype.
In all patients, the expanded cell population expressed very low NKa against K562 cell targets, but this increased significantly with recombinant human interleukin-2 (rhIL-2) and phytohemagglutinin (PHA) activation. Recombinant human alpha-interferon (rhIFN-alpha) had no significant effect on NKa. Cells displayed normal tumor cell binding capacity but failed to release sufficient amounts of functionally active natural killer cytotoxic factor(s) (NKCFs) upon interaction with the NK-sensitive K562 cells targets. However, they did release soluble cytolytic molecules against K562 cells upon activation with PHA.
Our findings provide evidence that the defective NKa in LGL-PD patients with the aforementioned phenotype is probably due, at least in part, to the inability of expanded lymphocytes to release NKCFs upon interaction with NK-sensitive cell targets. Since recognition of target cells by patient lymphocytes is not disturbed and the cells are capable of producing NKCFs upon activation with PHA, it is probable that the cause of this abnormality is located at the level of the activation signal provided by the stimulatory target cells. Studies in subcellular level are certainly needed for a more precise determination of the underlying defect.
慢性大颗粒淋巴细胞增殖性疾病（LGL-PD）是具有大颗粒淋巴细胞（LGL）形态的细胞的克隆性扩增。在大多数情况下，增殖细胞同时表达抑制性/溶细胞性T细胞和自然杀伤（NK）细胞表面标志物，但也可能观察到其他细胞表型。已发现LGL-PD淋巴细胞缺乏或显示极低的自然杀伤细胞活性（NKa）。本文旨在研究5例具有CD3 +、CD8 +、CD57 +细胞表型的LGL-PD患者同质性群体中NKa受损的潜在机制。
在所有患者中，扩增的细胞群体对K562细胞靶标的NKa表达非常低，但用重组人白细胞介素-2（rhIL-2）和植物血凝素（PHA）激活后，NKa显著增加。重组人α干扰素（rhIFN-α）对NKa没有显著影响。细胞显示出正常的肿瘤细胞结合能力，但与NK敏感的K562细胞靶标相互作用时，未能释放足够量的具有功能活性的自然杀伤细胞毒性因子（NKCFs）。然而，在用PHA激活后，它们确实释放了针对K562细胞的可溶性溶细胞分子。
我们的研究结果表明，上述表型的LGL-PD患者中NKa缺陷可能至少部分归因于扩增的淋巴细胞在与NK敏感细胞靶标相互作用时无法释放NKCFs。由于患者淋巴细胞对靶细胞的识别未受干扰，且细胞在用PHA激活后能够产生NKCFs，因此这种异常的原因可能位于刺激靶细胞提供的激活信号水平。当然需要在亚细胞水平进行研究以更精确地确定潜在缺陷。
