Komiyama A, Kawai H, Yamada S, Aoyama K, Yamazaki M, Saitoh H, Miyagawa Y, Akabane T, Uehara Y
Blood. 1985 Jul;66(1):99-105.
Natural killer (NK) cell activity was measured by a 51Cr-release assay using K562 target cells in 12 neutropenic children. NK cell activity was depressed in four patients who had childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The percentage of lysis at a 40:1 effector-target ratio was 28.4% to 42.1% (P less than .001) of the normal lymphocyte value during the study period (32 to 40 months). NK cell activity was normal in the other eight children with chronic neutropenia without any of these neutrophil abnormalities: lazy leukocyte syndrome, Shwachman syndrome, or dysgammaglobulinemia type I with neutrophil defects. NK cell activity of the four patients was depressed at 5:1 to 40:1 effector-target ratios. The NK cells responded to in vitro interferon (IFN)-alpha and interleukin 2, as did normal lymphocytes, but the activated levels were still lower than those of normal lymphocytes (P less than .01). Because NK cells kill a target through recognition, binding, killing, and detaching, and they repeat this lytic sequence (ie, recycling), the localization of the NK cell defect was further analyzed in the four patients using both 51Cr-release and single cell-in-agarose assays. The patients' NK cells were normal in recognizing, binding, and killing a target but were defective in recycling; the estimated maximum recycling capacity (MRC) values in a four-hour assay were 1.8 to 2.4 (P less than .01), as compared with the normal lymphocyte value of 5.5 +/- 0.6 (mean +/- SD). The stimulation of the effector cells with 1,000 U/mL IFN-alpha did not significantly increase the estimated MRC. These results demonstrate that NK cells are defective in recycling in some type of childhood chronic neutropenia with abnormal neutrophil morphology and chemotaxis. The NK cell deficiency is of clinical interest in terms of its relationship to the recurrent infections, development of malignancy, and dysgranulopoiesis in the disorder.
采用51Cr释放试验，以K562靶细胞检测了12例中性粒细胞减少儿童的自然杀伤（NK）细胞活性。4例患有儿童慢性中性粒细胞减少症且中性粒细胞形态和趋化性异常的患者，其NK细胞活性降低。在研究期间（32至40个月），效应细胞与靶细胞比例为40:1时的裂解百分比为正常淋巴细胞值的28.4%至42.1%（P小于0.001）。另外8例患有慢性中性粒细胞减少症且无任何中性粒细胞异常（如懒惰白细胞综合征、施瓦茨曼综合征或伴有中性粒细胞缺陷的I型免疫球蛋白异常血症）的儿童，其NK细胞活性正常。4例患者在效应细胞与靶细胞比例为5:1至40:1时，NK细胞活性降低。与正常淋巴细胞一样，NK细胞对体外干扰素（IFN）-α和白细胞介素2有反应，但激活水平仍低于正常淋巴细胞（P小于0.01）。由于NK细胞通过识别、结合、杀伤和分离来杀死靶细胞，并重复这种裂解序列（即循环利用），因此使用51Cr释放试验和单细胞琼脂糖试验对这4例患者NK细胞缺陷的定位进行了进一步分析。患者的NK细胞在识别、结合和杀伤靶细胞方面正常，但在循环利用方面存在缺陷；在4小时试验中，估计的最大循环利用能力（MRC）值为1.8至2.4（P小于0.01），而正常淋巴细胞值为5.5±0.6（平均值±标准差）。用1000 U/mL IFN-α刺激效应细胞，并未显著提高估计的MRC。这些结果表明，在某些伴有中性粒细胞形态和趋化性异常的儿童慢性中性粒细胞减少症中，NK细胞在循环利用方面存在缺陷。就其与该疾病中反复感染、恶性肿瘤发生和粒细胞生成异常的关系而言，NK细胞缺陷具有临床意义。
