Papadaki H A, Coulocheri S, Xylouri I, Chatzivassili A, Konsolas J, Katrinakis G, Karkavitsas N, Eliopoulos G D
Department of Hematology of the University of Crete School of Medicine, University Hospital of Heraklion, Greece.
Ann Hematol. 1998 Mar-Apr;76(3-4):127-34. doi: 10.1007/s002770050376.
Natural killer cell activity (Nka) of peripheral blood mononuclear cells (PBMCs) against K562 cell targets was assessed in 66 patients with chronic idiopathic neutropenia of adults (CINA) using the 16-h 51Cr-release assay. It was found that CINA patients exhibited significantly lower Nkr than normal subjects, which strongly correlated with the degree of neutropenia and the numbers of circulating neutrophils. Patients' NKa was increased by recombinant human interleukin-2 (rhIL-2) or recombinant human interferon-alpha (rhIFN-alpha), but the values obtained did not reach the respective NKa values found in normals. However, percentages of cytokine-induced rises of NKa did not differ statistically between patients and normal subjects. No serum inhibitors of NKa were demonstrated in our patients. CINA patients had low numbers of circulating NK cells as defined by the expression of NK-cell-related surface markers CD16, CD56, and CD57. CD16+ and CD56+, but not CD57+, cells correlated with the values of baseline NKa. The numbers of all these cell subsets correlated with the degree of neutropenia and the numbers of circulating neutrophils. Using CD56+-enriched PBL suspensions, it was shown that patients' NK cells displayed normal tumor cell binding capacity and produced in vitro normal amounts of natural killer cytotoxic factor(s) against K562 cell targets upon activation with rhIFN-alpha. Finally, percentages of perforin-expressing and granzyme B-expressing CD16+ cells did not differ statistically between patients and normal controls. Based on all these observations, we concluded that CINA patients display low NKa probably because they have low numbers of circulating NK cells. No functional abnormalities of NK cells were demonstrated. The cause and the underlying mechanisms leading to NK-cell depletion in these patients remain to be clarified.
采用16小时51Cr释放试验，对66例成人慢性特发性中性粒细胞减少症（CINA）患者外周血单个核细胞（PBMC）针对K562细胞靶标的自然杀伤细胞活性（Nka）进行了评估。结果发现，CINA患者的Nkr显著低于正常受试者，且与中性粒细胞减少程度和循环中性粒细胞数量密切相关。重组人白细胞介素-2（rhIL-2）或重组人干扰素-α（rhIFN-α）可使患者的NKa升高，但所获值未达到正常受试者的相应NKa值。然而，细胞因子诱导的NKa升高百分比在患者和正常受试者之间无统计学差异。在我们的患者中未发现NKa的血清抑制剂。根据NK细胞相关表面标志物CD16、CD56和CD57的表达情况定义，CINA患者循环NK细胞数量较少。CD16+和CD56+细胞（而非CD57+细胞）与基线NKa值相关。所有这些细胞亚群的数量均与中性粒细胞减少程度和循环中性粒细胞数量相关。使用富含CD56+的外周血淋巴细胞（PBL）悬液表明，患者的NK细胞具有正常的肿瘤细胞结合能力，在用rhIFN-α激活后，体外针对K562细胞靶标产生正常量的自然杀伤细胞毒性因子。最后，患者和正常对照之间表达穿孔素和颗粒酶B的CD16+细胞百分比无统计学差异。基于所有这些观察结果，我们得出结论，CINA患者的NKa较低可能是因为他们循环NK细胞数量较少。未发现NK细胞存在功能异常。导致这些患者NK细胞耗竭的原因及潜在机制仍有待阐明。
