Klimpel G R, Herndon D H, Stein M D
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
J Clin Immunol. 1988 Jan;8(1):14-22. doi: 10.1007/BF00915152.
We have previously shown that natural killer (NK) cell activity against K562 tumor cells is severely depressed in thermal injury patients. In this study we have investigated whether the low NK cell activity present in peripheral blood lymphocytes (PBL) from thermal injury patients could be enhanced by in vitro culture with interleukin 2 (IL2) and whether PBL obtained from these patients could generate lymphokine-activated killer (LAK) cell activity against NK insensitive tumor targets. NK cell activity in PBL obtained from 12 different patients was greatly enhanced against K562 tumor cells after in vitro culture with IL2 for 3 days. In contrast, PBL obtained from these patients and incubated with IL2 had little to no cytotoxic activity when measured against a number of NK-insensitive tumor targets. The failure of PBL obtained from thermal injury patients to generate LAK cell activity was observed regardless of the culture time or the amount of IL2 added to the cultures. PBL from thermal injury patients demonstrated reduced proliferative responses to IL2 and, more importantly, contained suppressor cells which could inhibit the generation of LAK cell activity of normal PBL obtained from control individuals. These results clearly show that in some thermal injury patients NK cell activity can be enhanced by IL2 but these patients are defective in their ability to generate LAK cell activity.
我们之前已经表明,热损伤患者对K562肿瘤细胞的自然杀伤(NK)细胞活性严重降低。在本研究中,我们调查了热损伤患者外周血淋巴细胞(PBL)中存在的低NK细胞活性是否可以通过白细胞介素2(IL2)体外培养来增强,以及从这些患者获得的PBL是否可以产生针对NK不敏感肿瘤靶标的淋巴因子激活的杀伤(LAK)细胞活性。用IL2体外培养3天后,从12名不同患者获得的PBL中针对K562肿瘤细胞的NK细胞活性大大增强。相比之下,从这些患者获得并与IL2孵育的PBL在针对许多NK不敏感肿瘤靶标进行检测时几乎没有细胞毒性活性。无论培养时间或添加到培养物中的IL2量如何,均观察到热损伤患者获得的PBL未能产生LAK细胞活性。热损伤患者的PBL对IL2的增殖反应降低,更重要的是,含有可以抑制从对照个体获得的正常PBL的LAK细胞活性产生的抑制细胞。这些结果清楚地表明,在一些热损伤患者中,NK细胞活性可以通过IL2增强,但这些患者在产生LAK细胞活性的能力方面存在缺陷。