Giacomelli R, Passacantando A, Frieri G, Parzanese I, D'Alò S, Vernia P, Pimpo M T, Petrucci C, Caprilli R, Cifone M G, Tonietti G
Department of Internal Medicine, Immunology Section and Gastroenterology Section and Department of Experimental Medicine, University of L'Aquila, Italy.
Clin Exp Immunol. 1999 Jan;115(1):72-7. doi: 10.1046/j.1365-2249.1999.00741.x.
This study was performed in order to assess the cytotoxic activity, both natural (NK) and antibody-dependent (ADCC), of PBMC from 38 IBD patients and correlate it with their clinical features. Cytotoxicity assays were performed using sensitive target cells for NK and ADCC activities. In some experiments, highly purified NK cells, obtained both by Percoll density gradient and by co-culturing non-adherent PBMC with RPMI 8866 feeder cells, were used as effector cells. Furthermore, we evaluated NK cell parameters such as number, surface expression of adhesion molecules (CD11a/CD18, CD49d and CD54) and response to different stimuli. We observed a decreased NK cytotoxicity of PBMC from IBD patients, both in ulcerative colitis (UC) and Crohn's disease (CD), independently of the clinical activity of disease. In contrast, the ADCC lytic activity was within normal range. The lower NK cytotoxic activity observed in our IBD patients cannot be related to a decreased number of NK cells, surface expression of adhesion molecules, defective response to IL-2 and maturative defect. Decreased NK activity was induced in PBMC of controls when serum of patients was added and this was unrelated to monocyte-derived modulating factor(s). Our data show a decreased natural killing by fresh PBMC from IBD patients. This lower activity seems to be unrelated to a primary NK cell defect, since purified NK cells exhibited normal levels of killing. It might be hypothesized that serum factors, possibly derived from lymphocytes, with inhibitory properties on NK activity, might be functionally active in the blood of IBD patients, thus modulating NK activity.
本研究旨在评估38例炎症性肠病（IBD）患者外周血单个核细胞（PBMC）的天然（NK）和抗体依赖性（ADCC）细胞毒性活性，并将其与患者的临床特征相关联。使用对NK和ADCC活性敏感的靶细胞进行细胞毒性测定。在一些实验中，通过Percoll密度梯度法以及通过将非贴壁PBMC与RPMI 8866饲养细胞共培养获得的高度纯化的NK细胞用作效应细胞。此外，我们评估了NK细胞参数，如数量、黏附分子（CD11a/CD18、CD49d和CD54）的表面表达以及对不同刺激的反应。我们观察到，在溃疡性结肠炎（UC）和克罗恩病（CD）患者中，PBMC的NK细胞毒性均降低，且与疾病的临床活动无关。相比之下，ADCC裂解活性在正常范围内。在我们的IBD患者中观察到的较低的NK细胞毒性与NK细胞数量减少、黏附分子的表面表达、对白细胞介素-2的反应缺陷以及成熟缺陷无关。当加入患者血清时，对照组PBMC的NK活性降低，这与单核细胞衍生的调节因子无关。我们的数据显示IBD患者新鲜PBMC的天然杀伤作用降低。这种较低的活性似乎与原发性NK细胞缺陷无关，因为纯化后的NK细胞显示出正常的杀伤水平。可以推测，可能源自淋巴细胞的、对NK活性具有抑制特性的血清因子，可能在IBD患者血液中具有功能活性，从而调节NK活性。
