Department of Clinical and Experimental Oncology, Division of Bone Marrow Transplantation and Lymphoma, Comprehensive Cancer Centre, Maria Sklodowska-Curie Memorial Institute-Gliwice Branch, Gliwice, Poland.
Bone Marrow Transplant. 2010 Jun;45(6):1022-30. doi: 10.1038/bmt.2009.384. Epub 2010 Feb 1.
Alloreactivity of natural killer (NK) cells contributes to the GVL reaction after allogeneic hematopoietic SCT (allo-HSCT). However, various procedure-related factors may affect NK cell maturation and their ability to recognize and kill leukemic cells. In this study, we prospectively evaluated expression of NK cell inhibitory receptors in 83 adults treated with myeloablative, killer cell Ig-like receptor (KIR)-ligand-matched allo-HSCT. NK cell maturation was evaluated by comparing the phenotypic patterns after allo-HSCT with the donor ones. The frequencies of KIR3DL1 were comparable to the donor ones on day +28, while they decreased significantly starting from day +100. The expression of KIR2DL2/3 was significantly lower in patients compared with donors up to day +100. The expression of KIR2DL1, despite continues growth, remained significantly decreased for 1 year after allo-HSCT. NKG2A was over-expressed up to day +180. Within 1 year after allo-HSCT, the NK cell phenotypic pattern tended to recapitulate the donor type. The process was disturbed by the use of steroids with significant differences observed on days +56 (P=0.01) and +100 (P=0.04). Up to day +100, reconstitution of NK cell receptor repertoire correlated with the absolute numbers of circulating CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) cells. Our observations should be taken into account when trying to predict potential benefit from NK cell alloreactivity.
自然杀伤 (NK) 细胞的同种异体反应有助于异基因造血干细胞移植 (allo-HSCT) 后的移植物抗白血病 (GVL) 反应。然而，各种与程序相关的因素可能会影响 NK 细胞的成熟及其识别和杀死白血病细胞的能力。在这项研究中，我们前瞻性地评估了 83 例接受清髓性、杀伤细胞免疫球蛋白样受体 (KIR)-配体匹配 allo-HSCT 的成年人的 NK 细胞抑制性受体的表达。通过将 allo-HSCT 后的表型模式与供体进行比较来评估 NK 细胞的成熟。KIR3DL1 的频率在第 +28 天与供体相似，而从第 +100 天开始显著下降。与供体相比，患者的 KIR2DL2/3 表达在第 +100 天之前显著降低。尽管持续增长，但 KIR2DL1 的表达在 allo-HSCT 后 1 年内仍显著降低。NKG2A 表达上调至第 +180 天。在 allo-HSCT 后 1 年内，NK 细胞表型模式趋于重现供体类型。类固醇的使用干扰了这一过程，在第 +56 天（P=0.01）和第 +100 天（P=0.04）观察到显著差异。在第 +100 天之前，NK 细胞受体库的重建与循环 CD3(+)、CD3(+)CD4(+)和 CD3(+)CD8(+)细胞的绝对数量相关。在试图预测 NK 细胞同种异体反应的潜在益处时，应该考虑到我们的观察结果。
