Hercend T, Takvorian T, Nowill A, Tantravahi R, Moingeon P, Anderson K C, Murray C, Bohuon C, Ythier A, Ritz J
Blood. 1986 Mar;67(3):722-8.
To identify cells with potential antileukemia activity following bone marrow transplantation, we have monitored immunologic reconstitution in a patient with acute lymphocytic leukemia in second remission who received intensive chemotherapy and total body irradiation followed by infusion of allogeneic histocompatible marrow. Prior to transplantation, donor bone marrow cells were depleted of T lymphocytes by in vitro treatment with anti-T12 monoclonal antibody and rabbit complement. In the first 3 weeks following bone marrow transplantation, the predominant regenerating mononuclear cell population in peripheral blood exhibited a phenotype characteristic of natural killer (NK) cells. After 4 weeks, T lymphocytes became predominant, but NK cells persisted. Cultured peripheral blood lymphocytes obtained 12 weeks posttransplant were able to display significant cytotoxicity against leukemic blasts that had been cryopreserved at the time of relapse 5 months prior to bone marrow transplantation. To further characterize those cells with antileukemia activity, we used in vitro cloning techniques to identify four monoclonal populations, termed TC12, -48, -50, and -59, with strong antitumor activity. Cytogenetic analysis demonstrated that each clone was of donor origin. Phenotypic characterization showed that the four clones expressed NKH1A but did not express T3, T4, or T8 antigens. Three of the four clones expressed T11/E rosette antigen. Each clone exhibited strong cytotoxicity against genetically unrelated hematopoietic tumor cell lines such as K562, Molt-4, JM, and U937. In addition, we found that these patient clones were similar to cloned NK cells previously derived from normal individuals. Taken together, these results suggest that at least some clones with antileukemia activity following bone marrow transplantation are cells with NK-like function and phenotype. Functional analysis of these cytolytic cells in larger numbers of patients will be necessary to determine the clinical significance of this finding.
为了识别骨髓移植后具有潜在抗白血病活性的细胞，我们监测了一名处于第二次缓解期的急性淋巴细胞白血病患者的免疫重建情况。该患者接受了强化化疗和全身照射，随后输注了同种异体组织相容性骨髓。移植前，通过用抗T12单克隆抗体和兔补体进行体外处理，去除供体骨髓细胞中的T淋巴细胞。在骨髓移植后的前3周，外周血中主要的再生单核细胞群体表现出自然杀伤（NK）细胞的表型特征。4周后，T淋巴细胞占主导，但NK细胞持续存在。移植后12周获得的培养外周血淋巴细胞能够对在骨髓移植前5个月复发时冻存的白血病原始细胞显示出显著的细胞毒性。为了进一步表征那些具有抗白血病活性的细胞，我们使用体外克隆技术鉴定了四个具有强抗肿瘤活性的单克隆群体，分别称为TC12、-48、-50和-59。细胞遗传学分析表明每个克隆都来自供体。表型特征显示这四个克隆表达NKH1A，但不表达T3、T4或T8抗原。四个克隆中有三个表达T11/E玫瑰花结抗原。每个克隆对遗传上不相关的造血肿瘤细胞系如K562、Molt-4、JM和U937都表现出强细胞毒性。此外，我们发现这些患者克隆与先前从正常个体获得的克隆NK细胞相似。综上所述，这些结果表明骨髓移植后至少一些具有抗白血病活性的克隆是具有NK样功能和表型的细胞。对更多患者的这些溶细胞性细胞进行功能分析对于确定这一发现的临床意义是必要的。
