Hauch M, Gazzola M V, Small T, Bordignon C, Barnett L, Cunningham I, Castro-Malaspinia H, O'Reilly R J, Keever C A
Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
Blood. 1990 Jun 1;75(11):2250-62.
The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host-derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host-derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft.
对40例接受慢性粒细胞白血病（CML）移植的患者评估了自然杀伤（NK）细胞的抗白血病潜力，以确定NK细胞功能的差异是否与随后的白血病复发相关。在51Cr释放试验中，检测了患者及其供体的细胞对完全异基因CML靶细胞和培养的K562靶细胞的杀伤作用；检测了26例患者的细胞对移植前冷冻保存的宿主来源的CML靶细胞的杀伤作用。在所有进行的试验中，培养的CML靶细胞（K562）对新鲜分离的外周血淋巴细胞（PBL）高度敏感，对在含白细胞介素-2（IL-2）的培养基中培养的PBL更敏感。相比之下，未培养的CML靶细胞仅被一部分患者的IL-2激活细胞裂解。若存在对CML靶细胞的裂解活性，在骨髓移植后3周即可检测到，且在移植后整个时期都保持阳性。最佳裂解活性在培养的第一周内产生，培养基中需要≥250 U/mL的IL-2。对完全异基因和宿主来源的CML靶细胞的裂解活性似乎由CD16+和CD56+细胞介导，而非CD3+细胞。对异基因CML靶细胞的裂解作用存在差异，但患者可分为两组：对大多数检测靶细胞有裂解活性的患者和无裂解活性的患者。裂解活性差异的原因不能归因于靶细胞对裂解的敏感性、培养物中NK细胞的比例或培养物中NK细胞亚群的表型。当进行平行检测时，供体和受体培养物对宿主来源的CML靶细胞的裂解活性高度相关，表明NK细胞识别CML靶细胞的能力可能存在内在差异。对宿主来源的CML靶细胞未能产生裂解活性的患者的复发风险比具有针对宿主白血病裂解活性的患者显著增加。这些数据表明，旨在激活NK细胞的IL-2移植后免疫疗法可能会增强移植物的移植物抗白血病潜力。
