Stabile Helena, Nisti Paolo, Peruzzi Giovanna, Fionda Cinzia, Pagliara Daria, Brescia Pomonia Letizia, Merli Pietro, Locatelli Franco, Santoni Angela, Gismondi Angela
Dept. Molecular Medicine.
Istituto Italiano di Tecnologia.
Oncoimmunology. 2017 Aug 10;6(9):e1342024. doi: 10.1080/2162402X.2017.1342024. eCollection 2017.
We recently described the CD56CD16 subset of Natural Killer (NK) cells that both mediate cytotoxic activity and produce IFNγ, being more abundant in bone marrow (BM) than in peripheral blood (PB) of pediatric normal subjects. Given the multifunctional properties of this subset, we examined its development and functional recovery in a cohort of children undergoing α/β T-cell depleted HLA-haploidentical haematopoietic stem cell transplantation (HSCT). The results obtained indicate that CD56CD16 NK cells are present in both PB and BM already at one month post-HSCT, with an increased frequency in BM of graft recipients as compared with normal subjects. During the first 6 months after HSCT, no difference in CD56CD16 NK cells distribution between PB and BM was observed. In comparison to normal subjects, CD56CD16 NK cells from transplanted patients show lower expression levels of CD25 and CD127 and higher levels of CD122, and accordingly, produce higher amounts of IFNγ after stimulation with IL-12 plus IL-15. The recovery of NK-cell cytotoxicity after HSCT was strictly restricted to CD56CD16 NK cells, and their ability to degranulate against K562 target cells or autologous leukemic blasts was completely restored only one year after HSCT. Based on the phenotypic and functional ability of reconstituted CD56CD16 NK cells, we suggest that they play an important role in host defense against leukemia relapse and infections after HSCT, and represent an ideal candidate for approaches of adoptive immunotherapy.
我们最近描述了自然杀伤（NK）细胞的CD56CD16亚群，该亚群既能介导细胞毒性活性又能产生干扰素γ，在儿科正常受试者的骨髓（BM）中比外周血（PB）中更为丰富。鉴于该亚群的多功能特性，我们在一组接受α/β T细胞去除的HLA单倍型造血干细胞移植（HSCT）的儿童中研究了其发育和功能恢复情况。获得的结果表明，HSCT后1个月时，PB和BM中均已存在CD56CD16 NK细胞，与正常受试者相比，移植受者BM中的频率增加。在HSCT后的前6个月，未观察到PB和BM之间CD56CD16 NK细胞分布的差异。与正常受试者相比，移植患者的CD56CD16 NK细胞显示出较低的CD25和CD127表达水平以及较高的CD122水平，因此，在用IL-12加IL-15刺激后产生更高量的干扰素γ。HSCT后NK细胞细胞毒性的恢复严格限于CD56CD16 NK细胞，并且它们对K562靶细胞或自体白血病母细胞脱颗粒的能力仅在HSCT后一年才完全恢复。基于重构的CD56CD16 NK细胞的表型和功能能力，我们认为它们在宿主抵抗HSCT后白血病复发和感染中起重要作用，并且是过继免疫治疗方法的理想候选者。
