Lotzová E
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston.
Med Oncol Tumor Pharmacother. 1989;6(1):93-8. doi: 10.1007/BF02985229.
We have shown that the patients with myelogenous leukemia display several defects in the NK cell lytic mechanism. However, this cytotoxic defect could be corrected after culture of effector cells from these patients with IL-2. The cytotoxic potential of IL-2-activated killer cells could be further augmented by treatment with OKT3 monoclonal antibody. Interleukin-2-activated lymphocytes were effective in killing not only a variety of tumor cell lines, but also autologous leukemic cells. Moreover, these cells were not stationary, but proliferated actively in culture with IL-2. Characterization studies, using the monoclonal antibodies against NK cell (CD16 and NKH1/Leu-19) or T-cell (CD3 and CD5) surface molecules showed that the antileukemia-directed cytotoxic cells were NK cells and not T-cells. In contrast, the T-cells (and not NK cells) exhibited an ability to down-regulate clonogenic activity of hematopoietic progenitors and to inhibit proliferation of bone marrow cells. Our data suggest that adoptive therapy with highly-enriched IL-2-activated NK cells may result in more powerful anti-leukemia effect. Alternatively, activated NK cells may be effective in eradication of leukemic cells from bone marrow for autologous bone marrow transplantation purposes.
我们已经表明，髓性白血病患者的自然杀伤（NK）细胞溶解机制存在一些缺陷。然而，用白细胞介素-2（IL-2）培养这些患者的效应细胞后，这种细胞毒性缺陷可以得到纠正。用OKT3单克隆抗体处理可进一步增强IL-2激活的杀伤细胞的细胞毒性潜力。IL-2激活的淋巴细胞不仅能有效杀伤多种肿瘤细胞系，还能杀伤自体白血病细胞。此外，这些细胞并非静止不动，而是在有IL-2的培养物中积极增殖。使用针对NK细胞（CD16和NKH1/Leu-19）或T细胞（CD3和CD5）表面分子的单克隆抗体进行的特性研究表明，抗白血病定向细胞毒性细胞是NK细胞而非T细胞。相反，T细胞（而非NK细胞）表现出下调造血祖细胞集落形成活性和抑制骨髓细胞增殖的能力。我们的数据表明，采用高度富集的IL-2激活的NK细胞进行过继性治疗可能会产生更强的抗白血病效果。或者，激活的NK细胞可能对从骨髓中清除白血病细胞以用于自体骨髓移植有效。
