Riccardi C, Giampietri A, Migliorati G, Cannarile L, D'Adamio L, Herberman R B
Int J Cancer. 1986 Oct 15;38(4):553-62. doi: 10.1002/ijc.2910380416.
The possible effect of IL-2, alpha,beta-IFN and poly I:C (an IFN inducer) administration on the generation of NK cells of LI and BM-reconstituted animals was investigated. B6D2F1 mice were LI (9.5 Gy) by total-body irradiation and reconstituted by i.v. injection of different doses (ranging from 10(6) to 2 X 10(7)) of syngeneic BM, after which the levels of splenic NK activity were evaluated on days 4, 7, 9, 12 and 14 after LI and BM graft. After a marked decline on day 4 (no detectable NK activity at any effector to target ratio tested), NK activity gradually returned, reaching the levels of untreated controls on day 9. Groups of LI and BM-reconstituted mice were also treated i.p. with mouse or human recombinant IL-2 from day 0 through day 3 (15-50 U/day/mouse) after BM transplantation. It appears that an earlier reconstitution of NK activity occurs in IL-2-treated animals as compared to medium-injected controls. LI and BM-reconstituted animals were also treated i.p. with alpha,beta-IFN (10(4) U/mouse) or Poly I:C (1 mg/kg/mouse) from day 0 through day 3, and the splenic NK activity was evaluated at 4, 7, 9, 12 and 14 days after LI and BM graft. Our data indicate that in vivo administration of IFN or Poly I:C was able to cause an earlier maturation of NK activity as measured on days 7 and 9 after LI. In contrast, when the NK activity of IFN-treated animals was compared with that of controls 14 days after LI and BM graft, a significant inhibition was found due to the induction of suppressor cells. Pre-treatment of donor BM with Poly I:C or IFN was also able to induce a more rapid reconstitution of NK activity of recipient mice. The NK activity reconstitution paralleled the increase in the number of splenic LGL. A synergistic effect was obtained when LI mice were transplanted with Poly I:C-pre-treated BM and then treated with IL-2. The effector cell in the IFN and IL-2 treated chimeras is a typical NK cell: asialo GM-1+, Thy 1 +/-, Lyt 1-, Lyt 2- and reactive only against NK-susceptible targets. These data suggest that IL-2 as well as IFN may represent maturational signals in the in vivo physiological regulation of growth and differentiation of BM NK stem-cells.
研究了给予白细胞介素-2（IL-2）、α、β干扰素（IFN）和聚肌胞苷酸（poly I:C，一种IFN诱导剂）对肝脏照射（LI）和骨髓重建动物自然杀伤（NK）细胞生成的可能影响。用全身照射使B6D2F1小鼠接受9.5 Gy的LI，并通过静脉注射不同剂量（范围从10⁶到2×10⁷）的同基因骨髓进行重建，之后在LI和骨髓移植后的第4、7、9、12和14天评估脾脏NK活性水平。在第4天显著下降后（在任何测试的效应细胞与靶细胞比例下均未检测到NK活性），NK活性逐渐恢复，在第9天达到未处理对照的水平。在骨髓移植后从第0天到第3天，对LI和骨髓重建的小鼠组腹腔注射小鼠或人重组IL-2（15 - 50 U/天/小鼠）。与注射培养基的对照相比，似乎在接受IL-2治疗的动物中NK活性更早恢复。在骨髓移植后从第0天到第3天，对LI和骨髓重建的动物腹腔注射α、β干扰素（10⁴ U/小鼠）或聚肌胞苷酸（1 mg/kg/小鼠），并在LI和骨髓移植后的第4、7、9、12和14天评估脾脏NK活性。我们的数据表明，在LI后第7天和第9天测量时，体内给予IFN或聚肌胞苷酸能够使NK活性更早成熟。相反，当在LI和骨髓移植后14天比较IFN治疗动物与对照的NK活性时，发现由于抑制细胞的诱导有显著抑制作用。用聚肌胞苷酸或IFN对供体骨髓进行预处理也能够诱导受体小鼠NK活性更快重建。NK活性重建与脾脏大颗粒淋巴细胞（LGL）数量增加平行。当LI小鼠移植用聚肌胞苷酸预处理的骨髓然后用IL-2治疗时获得协同效应。在IFN和IL-2治疗的嵌合体中的效应细胞是典型的NK细胞：无唾液酸神经节苷脂-1阳性、Thy 1 +/ -、Lyt 1阴性、Lyt 2阴性且仅对NK敏感靶标有反应。这些数据表明，IL-2以及IFN可能代表骨髓NK干细胞生长和分化的体内生理调节中的成熟信号。
