Chikkala N F, Lewis I, Ulchaker J, Stanley J, Tubbs R, Finke J H
Department of Immunology and Cancer, Cleveland Clinic Foundation, Ohio 44195.
Cancer Res. 1990 Feb 15;50(4):1176-82.
Studies from our laboratory and others have demonstrated that alpha-interferon (IFN alpha) can regulate natural killer cells and lymphokine-activated killer (LAK) cell activation. In vitro experiments have shown that IFN alpha has differential effects on both natural killer cells and LAK activity when combined with interleukin 2 (IL2); IFN alpha synergized with IL2 to augment natural killer cells activity while it suppressed the IL2-induced LAK response. Here we demonstrated that IFN alpha A/D can also regulate IL2-induced LAK activity in vivo with enhanced or suppressed activity depending on the IFN alpha A/D dose. The enhanced response was observed with the combination when 80,000 units/day of IFN alpha A/D were used and was detectable in the spleen, lung, and peritoneum. When a high dose of IFN alpha A/D was combined with IL2, a moderate reduction in LAK activity was noted in the spleen and peritoneum. In contrast, a high dose IFN alpha A/D augmented IL2-induced LAK activity in the lung even though it reduced the level of cellular infiltration. We have also evaluated the effect that IL2, IFN alpha A/D, and IL2 plus IFN alpha A/D have on the frequency of LAK precursors in the spleen and lung using limiting dilution analysis. Treatment of normal mice with IL2 alone increased the frequency of LAK precursor (LAKp) in the lung. This increase was associated with an infiltration of Thy-1+, asialo-GM1+, Lyt-2- lymphocytes into the lungs. Moreover, treatment with IL2 plus IFN alpha A/D enhanced the frequency of LAKp over that observed with IL2 alone. Treatment with the combination did not change the phenotype of LAKp in the lung from that seen with IL2. The increase in LAKp frequency induced by the combined treatment may not be a direct effect of IFN alpha A/D on precursor cells since IFN alpha A/D alone did not increase the frequency of LAKp in vivo or in vitro when added to limiting dilution analysis cultures. In contrast to what occurred in the lung, a consistent increase in LAKp was not seen in the spleen after treatment with IL2 or with the combination, although LAK activity was observed. These results demonstrated that in addition to inducing lytic activity from LAK effectors in vivo, IL2 treatment increased the number of precursor cells within the lung. Moreover, IFN alpha A/D in combination with IL2 influenced the level of LAKp in situ.
我们实验室及其他机构的研究表明，α-干扰素（IFNα）可调节自然杀伤细胞和淋巴因子激活的杀伤（LAK）细胞的活化。体外实验显示，IFNα与白细胞介素2（IL2）联合使用时，对自然杀伤细胞和LAK活性具有不同的影响；IFNα与IL2协同增强自然杀伤细胞活性，同时抑制IL2诱导的LAK反应。在此，我们证明IFNα A/D在体内也可调节IL2诱导的LAK活性，其活性增强或受到抑制取决于IFNα A/D的剂量。当使用80,000单位/天的IFNα A/D时，联合使用可观察到增强的反应，且在脾脏、肺和腹膜中均可检测到。当高剂量的IFNα A/D与IL2联合使用时，脾脏和腹膜中的LAK活性出现适度降低。相反，高剂量的IFNα A/D虽降低了细胞浸润水平，但增强了肺中IL2诱导的LAK活性。我们还使用极限稀释分析评估了IL2、IFNα A/D以及IL2加IFNα A/D对脾脏和肺中LAK前体细胞频率的影响。单独用IL2处理正常小鼠可增加肺中LAK前体细胞（LAKp）的频率。这种增加与Thy-1 +、无唾液酸GM1 +、Lyt-2 -淋巴细胞浸润到肺中有关。此外，与单独使用IL2相比，IL2加IFNα A/D处理可提高LAKp的频率。联合处理并未改变肺中LAKp的表型，与单独使用IL2时所见相同。联合处理诱导的LAKp频率增加可能不是IFNα A/D对前体细胞的直接作用，因为在极限稀释分析培养物中单独添加IFNα A/D时，在体内或体外均未增加LAKp的频率。与肺中的情况相反，用IL2或联合处理后，脾脏中虽观察到LAK活性，但LAKp并未持续增加。这些结果表明，除了在体内诱导LAK效应细胞的溶解活性外，IL2处理还增加了肺中前体细胞的数量。此外，IFNα A/D与IL2联合影响了原位LAKp的水平。
