Cervantes F, Miller J S, McGlave P B
Escuela de Hematología Farreras Valentí. Servicio de Hematología, Hospital Clínic i Provincial, Barcelona.
Med Clin (Barc). 1995 Jun 10;105(2):50-3.
Recent studies indicate that patients with chronic myeloid leukemia (CML) have a population of benign cytolytic cells (natural killer or NK) in their peripheral blood which may expand and activate in vitro in the presence of interleukin-2 (IL-2) leading to cytolytic cells activated by lymphokine or LAK cells (lymphokine-activated killer).
Thirteen patients with CML in the chronic phase of a median of 8 months (range: 1-43) in length and 13 healthy individuals were studied. The NK cells were separated from the peripheral blood by centrifugation by density gradient, elutriation and depletion in flasks with the CD5 and CD8 monoclonal antibodies. The resulting cell solution was cultivated in medium with IL-2 (1,000 U/ml) for 16 days with the count, phenotypic study and cytotoxicity tests of non adherent cells (LAK) being thereafter performed.
Following the separation, the CD56+/CD3- cells constituted 6.9 +/- 2.4% of the total of the patients with CML. At day 16 of the culture, the non adherent cells of the CD56+/CD3- phenotype (LAK cells) were found to be 57.9 +/- 4.4% of the total (expansion = 31 +/- 10.4 fold with respect to the initial number of NK cells). The LAK cells showed intense cytotoxic activity versus the killer-sensitive K562 cell lines (76.2 +/- 4.2% of lysis to the effector/target cell proportion 20:1 and 5.6 +/- 1.3% to the proportion 0.08:1) and Raji killer-resistant (65.7 +/- 4.3% and 3.8 +/- 1.6%, respectively). Thus, the grade of LAK cell expansion and their cytotoxicity in patients with CML were significantly lower than in healthy individuals.
Chronic phase patients with chronic myeloid leukemia may generate, in vitro, a population of LAK cells with intense cytotoxic activity in the peripheral blood.
近期研究表明,慢性髓性白血病(CML)患者外周血中存在一群良性溶细胞性细胞(自然杀伤细胞或NK细胞),在白细胞介素-2(IL-2)存在的情况下,这些细胞可能在体外扩增并激活,从而产生淋巴因子激活的杀伤细胞(LAK细胞)。
对13例处于慢性期、病程中位数为8个月(范围:1 - 43个月)的CML患者和13名健康个体进行研究。通过密度梯度离心、淘析以及用CD5和CD8单克隆抗体在培养瓶中去除细胞等方法,从外周血中分离出NK细胞。将所得细胞悬液在含IL-2(1000 U/ml)培养基中培养16天,之后对非贴壁细胞(LAK细胞)进行计数、表型研究和细胞毒性测试。
分离后,CD56⁺/CD3⁻细胞占CML患者细胞总数的6.9±2.4%。培养至第16天时,发现CD56⁺/CD3⁻表型的非贴壁细胞(LAK细胞)占细胞总数的57.9±4.4%(相对于初始NK细胞数量扩增了31±10.4倍)。LAK细胞对杀伤敏感的K562细胞系显示出强烈的细胞毒性活性(效应细胞/靶细胞比例为20:1时,裂解率为76.2±4.2%;比例为0.08:1时,裂解率为5.6±1.3%),对Raji杀伤抗性细胞系的裂解率分别为65.7±4.3%和3.8±1.6%。因此,CML患者中LAK细胞的扩增程度及其细胞毒性显著低于健康个体。
慢性髓性白血病慢性期患者外周血在体外可产生具有强烈细胞毒性活性的LAK细胞群体。