Stabile Helena, Nisti Paolo, Morrone Stefania, Pagliara Daria, Bertaina Alice, Locatelli Franco, Santoni Angela, Gismondi Angela
Department Molecular Medicine, University of Rome "La Sapienza"
Department Experimental Medicine, University of Rome "La Sapienza"
Haematologica. 2015 Apr;100(4):489-98. doi: 10.3324/haematol.2014.116053. Epub 2015 Jan 16.
We phenotypically and functionally characterized a distinct CD56(low) natural killer cell subset based on CD16 expression levels in bone marrow and peripheral blood of healthy children and pediatric patients with acute lymphoblastic leukemia. Our findings demonstrate for the first time that CD56(low)CD16(low) natural killer cells are more abundant in bone marrow than in peripheral blood and that their frequency is further increased in children with acute lymphoblastic leukemia. Bone marrow and peripheral blood CD56(low)CD16(low) natural killer cells compared with CD56(low)CD16(high) natural killer cells express lower levels of killer inhibitory receptors, higher levels of CD27, CD127, CD122, CD25, but undetectable levels of CD57, suggesting that they have a higher proliferative and differentiation potential. Moreover, CD56(low)CD16(low) natural killer cells display higher levels of CXCR4 and undetectable levels of CX3CR1 and can be consistently and rapidly mobilized in peripheral blood in response to CXCR4 antagonist. Unlike CD56(low)CD16(high), both bone marrow and peripheral blood CD56(low)CD16(low) natural killer cells release IFNγ following cytokine stimulation, and represent the major cytotoxic natural killer cell population against K562 or acute lymphoblastic leukemia target cells. All these data suggest that CD56(low)CD16(low) natural killer cells are multifunctional cells, and that the presence of hematologic malignancies affects their frequency and functional ability at both tumor site and in the periphery.
我们根据健康儿童和急性淋巴细胞白血病患儿骨髓及外周血中CD16的表达水平，对一个独特的CD56（低）自然杀伤细胞亚群进行了表型和功能特征分析。我们的研究结果首次表明，CD56（低）CD16（低）自然杀伤细胞在骨髓中比在外周血中更为丰富，并且在急性淋巴细胞白血病患儿中其频率进一步增加。与CD56（低）CD16（高）自然杀伤细胞相比，骨髓和外周血中的CD56（低）CD16（低）自然杀伤细胞表达较低水平的杀伤抑制受体、较高水平的CD27、CD127、CD122、CD25，但检测不到CD57水平，这表明它们具有更高的增殖和分化潜能。此外，CD56（低）CD16（低）自然杀伤细胞显示出较高水平的CXCR4，检测不到CX3CR1水平，并且在响应CXCR4拮抗剂时可在外周血中持续且快速地动员。与CD56（低）CD16（高）不同，骨髓和外周血中的CD56（低）CD16（低）自然杀伤细胞在细胞因子刺激后都会释放IFNγ，并且是针对K562或急性淋巴细胞白血病靶细胞的主要细胞毒性自然杀伤细胞群体。所有这些数据表明，CD56（低）CD16（低）自然杀伤细胞是多功能细胞，并且血液系统恶性肿瘤的存在会影响它们在肿瘤部位和外周的频率及功能能力。
