Fujimiya Y, Wagner R J, Groveman S, Sielaff K, Kohsaka T, Nakayama M
Section of Immunology, Childrens' Medical Research Center, National Children's Hospital, Tokyo, Japan.
Ther Immunol. 1995 Feb;2(1):15-22.
Natural killer (NK) activity was assayed in fresh peripheral blood mononuclear cells (PBMs) from cancer patients receiving interferon (IFN)-beta ser. Patients received a single intravenous injection of IFN-beta ser (90 x 10(6) IU m-2) on alternate days for 2 weeks, followed by a higher dose (180 x 10(6) IU m-2) on the same schedule. PBM NK lysis of K562 target cells was significantly increased in PBMs sampled 24 h after the initial injection (P < 0.05). At the end of the first 2 weeks of the protocol, NK cytotoxic activity of PBMs had fallen below the original baseline levels; the higher IFN dose subsequently given was without effect. However, significant increases in the proportion of CD16+ cells were seen following each injection. A positive correlation was also seen between the increased lytic activity of CD16+ NK cells and the proportion of CD38+ NK cells, but not the proportion of CD56+ NK cells. In vitro IFN-treatment of these in vivo-treated PBMs resulted in a further increase in NK activity. Pre-exposure in vivo to IFN-beta ser seems to prime the PBMs to respond to in vitro stimulation by IFN-gamma, which otherwise had no effect. Phenotypic analysis of PBMs after in vitro exposure to IFN-beta ser showed that the levels of CD16+, CD38+ and CD56+ cells did not change. All the NK activity responding to IFN-beta ser was found in the CD16+ enriched population of PBM, suggesting that it is unlikely that in vivo redistribution of CD16+ subsets representative of NK cells has occurred in the peripheral blood.
对接受β-干扰素血清治疗的癌症患者的新鲜外周血单个核细胞（PBMs）进行自然杀伤（NK）活性检测。患者每隔一天接受一次β-干扰素血清的单次静脉注射（90×10⁶IU/m²），持续2周，之后按照相同的时间表给予更高剂量（180×10⁶IU/m²）。在首次注射后24小时采集的PBMs中，K562靶细胞的PBM NK裂解显著增加（P<0.05）。在方案的前2周结束时，PBMs的NK细胞毒性活性已降至原始基线水平以下；随后给予的更高剂量的干扰素没有效果。然而，每次注射后CD16⁺细胞比例均有显著增加。CD16⁺NK细胞裂解活性的增加与CD38⁺NK细胞的比例之间也存在正相关，但与CD56⁺NK细胞的比例无关。对这些经体内治疗的PBMs进行体外干扰素处理后，NK活性进一步增加。体内预先暴露于β-干扰素血清似乎使PBMs对γ-干扰素的体外刺激产生反应，否则γ-干扰素没有效果。体外暴露于β-干扰素血清后对PBMs进行表型分析表明，CD16⁺、CD38⁺和CD56⁺细胞的水平没有变化。所有对β-干扰素血清有反应的NK活性都存在于PBM中富含CD16⁺的群体中，这表明外周血中不太可能发生代表NK细胞的CD16⁺亚群的体内重新分布。
