Kiladjian J-J, Bourgeois E, Lobe I, Braun T, Visentin G, Bourhis J-H, Fenaux P, Chouaib S, Caignard A
INSERM U487, Institut Gustave Roussy, Villejuif, France.
Leukemia. 2006 Mar;20(3):463-70. doi: 10.1038/sj.leu.2404080.
Natural Killer (NK) cells are critical in host defense against malignant transformation and are potent antileukemic cytotoxic effectors. In the present study, we investigated the peripheral NK function in patients with myelodysplastic syndromes (MDS). We demonstrated that the peripheral NK cell population was quantitatively normal in MDS patients. Furthermore, NK cells displayed an expression of the activating natural cytotoxicity receptors (NCR) NKp46 and NKp30 as well as NKG2D similar to that observed in donors, but exert a highly decreased constitutive cytolytic activity compared to resting normal NK cells. Although activation with IL-2 resulted in the upregulation of NKp46 expression by MDS-NK cells, their cytolytic function remained deeply altered as compared to activated donor NK cells. In addition, MDS NK cells did not proliferate in vitro, and displayed an increased rate of apoptosis in response to IL-2 stimulation although the spontaneous apoptosis was not significantly increased. Interestingly, a proportion of peripheral MDS-NK cells were derived from the MDS clone as the cytogenetic anomaly found in bone marrow karyotype was also detected in 20-50% of circulating NK cells. In conclusion, NK cells' cytolytic function and proliferative capacities in response to activation by cytokines are profoundly altered in MDS.
自然杀伤（NK）细胞在宿主抵御恶性转化过程中至关重要，是强大的抗白血病细胞毒性效应细胞。在本研究中，我们调查了骨髓增生异常综合征（MDS）患者的外周血NK功能。我们发现，MDS患者外周血NK细胞数量正常。此外，NK细胞表达活化性自然细胞毒性受体（NCR）NKp46和NKp30以及NKG2D，与供体中的情况相似，但与静息正常NK细胞相比，其组成性细胞溶解活性显著降低。尽管用白细胞介素-2（IL-2）激活可导致MDS-NK细胞中NKp46表达上调，但其细胞溶解功能与活化的供体NK细胞相比仍有很大改变。此外，MDS-NK细胞在体外不增殖，对IL-2刺激的反应中凋亡率增加，尽管自发凋亡没有显著增加。有趣的是，一部分外周血MDS-NK细胞来源于MDS克隆，因为在20%-50%的循环NK细胞中也检测到了骨髓核型中的细胞遗传学异常。总之，在MDS中，NK细胞对细胞因子激活的细胞溶解功能和增殖能力发生了深刻改变。
