Lotzová E, Savary C A, Schachner J R, Huh J O, McCredie K
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Am J Hematol. 1991 Jun;37(2):88-99. doi: 10.1002/ajh.2830370206.
We have studied the cytotoxic profile and distribution of lymphocyte subsets of patients with acute myelogenous leukemia in second remission, after continuous infusion with recombinant interleukin-2 (IL-2). The patients received repetitive cycles of 1-1.25 x 10(6) U/m2/day of IL-2, given as 4 days continuous intravenous infusion followed by a 3-day treatment-free interval for the first 4 weeks. Patients receiving greater than 4 cycles were treated with the same dose of IL-2 continuously for 4 days, followed by a 10-day treatment-free interval. These studies showed that IL-2 treatment resulted in the generation of peripheral blood cytotoxic activity against both NK-susceptible, K-562, and NK-resistant Daudi cell lines. In most patients, enhancement of lytic activity increased with the number of IL-2 infusions. The cytotoxicity in some patients increased as much as 700-fold and 830-fold against K-562 and Daudi cells, respectively. It is of importance that oncolytic activity was also induced in bone marrow compartment (up to 182-fold against K-562). Some decline in cytotoxicity was observed within 14 days after initiation of IL-2 infusion in peripheral blood, but high levels of lytic activity persisted at this time in bone marrow. It is of interest to note that the cytotoxicity of in vivo IL-2 primed lymphocytes was further potentiated by IL-2 in vitro. Importantly, the cytotoxic cells induced in vitro displayed lytic activity against fresh leukemic blasts. Phenotypic analysis demonstrated that CD3-, CD56+ NK cells were significantly increased by in vivo IL-2 treatment (34 to 47-fold in absolute numbers), while CD3-, CD56+ T-cell subset remained low. Characterization of cytotoxic cells using the complement-dependent assay and monoclonal antibodies indicated that both the in vivo-induced and ex vivo-potentiated lytic function was mediated by CD3-, CD56+, CD16- -NK cells.
我们研究了急性髓性白血病患者在第二次缓解期连续输注重组白细胞介素-2（IL-2）后淋巴细胞亚群的细胞毒性特征和分布。患者接受1 - 1.25×10⁶ U/m²/天的IL-2重复疗程，最初4周以连续4天静脉输注给药，随后有3天无治疗间隔期。接受超过4个疗程的患者以相同剂量的IL-2连续治疗4天，随后有10天无治疗间隔期。这些研究表明，IL-2治疗导致外周血产生针对NK敏感的K-562细胞系和NK抗性的Daudi细胞系的细胞毒性活性。在大多数患者中，溶解活性的增强随着IL-2输注次数的增加而增加。一些患者对K-562和Daudi细胞的细胞毒性分别增加了多达700倍和830倍。重要的是，骨髓区室也诱导了溶瘤活性（对K-562高达182倍）。在IL-2输注开始后14天内，外周血中的细胞毒性有所下降，但此时骨髓中仍持续存在高水平的溶解活性。值得注意的是，体内IL-2预处理的淋巴细胞的细胞毒性在体外被IL-2进一步增强。重要的是，体外诱导的细胞毒性细胞对新鲜白血病原始细胞显示出溶解活性。表型分析表明，体内IL-2治疗使CD3⁻、CD56⁺ NK细胞显著增加（绝对数量增加34至47倍），而CD3⁻、CD56⁺ T细胞亚群仍然较低。使用补体依赖性测定和单克隆抗体对细胞毒性细胞进行表征表明，体内诱导和体外增强的溶解功能均由CD3⁻、CD56⁺、CD16⁻ NK细胞介导。
