Zambello R, Trentin L, Agostini C, Chisesi T, Vespignani M, Pizzolo G, Pandolfi F, Ensoli F, Semenzato G
Department of Clinical Medicine, University of Padua, Italy.
Leuk Res. 1989;13(4):315-22. doi: 10.1016/0145-2126(89)90068-4.
To further investigate the mechanisms accounting for defective natural killer (NK) activity observed in the majority of patients with lymphoproliferative disease of granular lymphocytes (LDGL), we have studied the generation of natural killer cytotoxic factor (NKCF) from peripheral blood lymphocytes recovered from twelve LDGL patients. On the basis of their cytotoxic activity against the K-562 target cells, cases under study were separated in two groups. Cells from five patients, referred to as NK+, were found to exhibit high levels of NK-cell mediated cytotoxicity; cells from seven patients, referred to as NK-, despite their ability to bind to the K-562 targets, displayed a defective NK function. The coculture of cells from NK+ patients with NK sensitive K-562 cells triggered a significantly higher production of NKCF with respect to NK- patients (p less than 0.001 at 1:2 dilution). Using phytohemagglutinin (PHA) as the NKCF stimulator, differences between the groups were not significant, due to a recovery of NKCF generation in NK- patients. Furthermore, a consistent lectin (PHA) dependent cellular cytotoxicity (LDCC) was exhibited by both groups of patients. The addition of gamma-interferon (IFN-gamma) or interleukin-2 (IL-2) during NKCF generation did not significantly modify the production of this factor. Our data point out that (a) NKCF is involved in the lytic activity of LDGL patients' cells, (b) a constitutional impairment in the generation of NKCF is not present in NK- patients, since recovery of lytic function occurs after PHA stimulation, and (c) IL-2 and IFN-gamma do not play a relevant role in triggering NKCF production when added during the generation of this factor. These studies help to clarify the factors involved in the cytotoxic machinery of LDGL patients' cells, suggesting that the defect of the cytotoxic function observed in some LDGL patients could lie at the level of target recognition.
为了进一步研究多数颗粒淋巴细胞增殖性疾病（LDGL）患者中自然杀伤（NK）活性缺陷的机制，我们研究了从12例LDGL患者外周血淋巴细胞中产生自然杀伤细胞毒性因子（NKCF）的情况。根据它们对K-562靶细胞的细胞毒性活性，将研究病例分为两组。来自5例患者的细胞，称为NK+，表现出高水平的NK细胞介导的细胞毒性；来自7例患者的细胞，称为NK-，尽管它们能够与K-562靶细胞结合，但显示出NK功能缺陷。与NK敏感的K-562细胞共培养时，NK+患者的细胞比NK-患者的细胞触发产生的NKCF显著更高（在1:2稀释时p小于0.001）。使用植物血凝素（PHA）作为NKCF刺激剂时，两组之间的差异不显著，因为NK-患者的NKCF产生有所恢复。此外，两组患者均表现出一致的凝集素（PHA）依赖性细胞毒性（LDCC）。在NKCF产生过程中添加γ干扰素（IFN-γ）或白细胞介素-2（IL-2）并没有显著改变该因子的产生。我们的数据表明：（a）NKCF参与LDGL患者细胞的裂解活性；（b）NK-患者不存在NKCF产生的先天性损害，因为PHA刺激后裂解功能恢复；（c）在NKCF产生过程中添加IL-2和IFN-γ在触发NKCF产生方面不起相关作用。这些研究有助于阐明LDGL患者细胞细胞毒性机制中涉及的因素，表明在一些LDGL患者中观察到的细胞毒性功能缺陷可能在于靶细胞识别水平。
