van de Loosdrecht A A, Ossenkoppele G J, Beelen R H, Broekhoven M G, Langenhuijsen M M
Department of Haematology, University Hospital, Amsterdam, The Netherlands.
Cancer Immunol Immunother. 1992;34(6):393-8. doi: 10.1007/BF01741750.
In view of cellular adoptive immunotherapy we have studied monocyte-mediated cytostasis and cytotoxicity against U 937 cells, a human histiocytic lymphoma cell line. Highly purified human monocytes and monocyte-derived macrophages were activated with interferon gamma (IFN) or tumour necrosis factor alpha (TNF) to antileukemic immune effector cells. Antileukemic activity of human monocytes was dependent on monocyte differentiation into macrophages and on a dose- and time-dependent activation with IFN or TNF. Maximum cytostasis of 97.0 +/- 0.7% (mean +/- SEM) (conventional [3H]dT uptake assay) and 81.9 +/- 5.3% cytotoxicity (modified MTT assay) of U 937 cells was obtained by monocytes activated with 100 U/ml IFN for at least 24 h at an effector-to-target-cell ratio of 10. U 937 cells premodified with IFN showed an increase in susceptibility to monocyte-mediated cytotoxicity. U 937 cells premodified with TNF were almost resistant to monocyte-mediated cytotoxicity while activated monocytes maintained their cytotoxic potential. These data show that IFN and TNF are potent activators of monocyte-mediated cytotoxicity. Furthermore, IFN and TNF might be involved in the regulation of the susceptibility of leukemic cells to lysis by interactions with monocytes or macrophages.
鉴于细胞过继性免疫疗法，我们研究了单核细胞对人组织细胞淋巴瘤细胞系U 937细胞的介导细胞生长抑制作用和细胞毒性。高度纯化的人单核细胞和单核细胞衍生的巨噬细胞用γ干扰素（IFN）或肿瘤坏死因子α（TNF）激活，成为抗白血病免疫效应细胞。人单核细胞的抗白血病活性取决于单核细胞分化为巨噬细胞以及IFN或TNF的剂量和时间依赖性激活。通过用100 U/ml IFN激活单核细胞至少24小时，效应细胞与靶细胞比例为10时，U 937细胞的最大细胞生长抑制率为97.0±0.7%（平均值±标准误）（传统的[3H]dT摄取试验），细胞毒性为81.9±5.3%（改良MTT试验）。用IFN预先处理的U 937细胞对单核细胞介导的细胞毒性的敏感性增加。用TNF预先处理的U 937细胞对单核细胞介导的细胞毒性几乎具有抗性，而激活的单核细胞保持其细胞毒性潜力。这些数据表明，IFN和TNF是单核细胞介导的细胞毒性的有效激活剂。此外，IFN和TNF可能通过与单核细胞或巨噬细胞相互作用参与白血病细胞对裂解敏感性的调节。
