成人传染性单核细胞增多症相关肝损伤患者自然杀伤细胞亚群的比例和功能变化  

The Change in Subpopulation and Function of Natural Killer Cells in Adult Patients with Infectious Mononucleosis Related Liver Injury

作　　者：侯环荣[1] 康谊[1] HOU Huan-Rong;KANG Yi(Deparoment of Infectious Diseases,Henan Provincial People's Hospital,Zhengzhou 450003,Henan Province,China)

机构地区：[1]河南省人民医院感染性疾病科,河南郑州450003

出　　处：《中国实验血液学杂志》2023年第4期1217-1223,共7页Journal of Experimental Hematology

摘　　要：目的:分析成人传染性单核细胞增多症(IM)相关肝损伤患者自然杀伤(NK)细胞亚群比例和功能的变化。方法:入组17例健康对照者、26例传染性单核细胞增多症无肝损伤患者、21例IM合并肝损伤患者,采集外周血,分离血浆和外周血单个核细胞(PBMC),酶联免疫吸附试验检测血浆白细胞介素-15(IL-15)水平,流式细胞术检测CD56^(+)CD16-、CD56^(+)CD16^(+)、CD56-CD16^(+)3个NK细胞亚群比例。PBMC分别与721.221细胞、K562细胞、P815-Ab细胞共培养,流式细胞术检测NK细胞中CD107a的表达和CD16平均荧光强度(MFI)。使用抗IL-15中和抗体刺激IM合并肝损伤患者PBMC,观察NK细胞功能变化。组间比较采用单因素方差分析或配对t检验。结果:CD56^(+)CD16-NK细胞在IM合并肝损伤组(7.36±0.92)%和IM无肝损伤组(10.67±1.37)%的比例均明显低于对照组(12.02±2.51)%(P<0.05),IM合并肝损伤组CD56^(+)CD16-NK细胞比例低于IM无肝损伤组(P<0.0001)。CD56^(+)CD16^(+)NK细胞在IM合并肝损伤组(62.03±8.78)%和IM无肝损伤组(44.74±13.03)%的比例高于对照组(40.74±10.15)%(P<0.05),IM合并肝损伤组CD56^(+)CD16^(+)NK细胞比例高于IM无肝损伤组(P<0.0001)。CD56-CD16^(+)NK细胞比例在3组之间的差异无统计学意义(P=0.427)。血浆IL-15在IM合并肝损伤组(309.1±68.00)pg/ml的水平明显高于IM无肝损伤组(269.6±53.57)pg/ml和对照组(257.4±73.93)pg/ml(P<0.05)。NK细胞通过不同受体介导杀伤相应靶细胞后,IM合并肝损伤组NK细胞中CD107a阳性细胞比例明显高于IM无肝损伤组和对照组(P<0.05),CD16 MFI明显低于IM无肝损伤组和对照组(P<0.05)。抗IL-15中和抗体刺激IM合并肝损伤患者PBMC后,NK细胞中CD107a比例明显降低(P<0.05)。结论:IM合并肝损伤患者中存在NK细胞亚群失衡和功能增强,IM合并肝损伤患者中IL-15水平升高可能增强NK细胞的毒性作用。Objective:To investigate the changes of subpopulation and function of natural killer(NK)cells in adult patients with infectious mononucleosis related liver injury.Methods:Seventeen healthy controls,twenty-six patients of infectious mononucleosis(IM)without liver injury,and twenty-one IM patients with liver injury were enrolled in this study.Peripheral blood was collected.Plasma and peripheral blood mononuclear cells(PBMC)were purified.Plasma interleukin-15(IL-15)level was measured by enzy me linked immunosorbent assay.Three NK cell subpopulations,including CD56^(+)CD16^(+),CD56^(+)CD16^(+),and CD56-CD16^(+)NK cells,were assessed by flow cytometry.PBMC were co-cultured with 721.221,K562,and P815-Ab cells,respectively.CD107a expression and CD16 mean fluorescence intensity(MFI)in NK cells was investigated by flow cytometry.PBMC from IM patients with liver injury were stimulated with anti-IL-15 neutralizing antibody,and the change of NK cell function was observed.One-way ANOVA and paired 1 test were used for statistical analysis.Results:The percentage of CD56^(+)CD16"NK cells in IM patients with liver injury(7.36+0.92)%and IM patients without liver injury(10.67+1.37)%were lower than that of controls(12.02+2.51)%(P<0.05).CD56^(+)CD16^(+)NK cell frequency in IM patients with liver injury also was lower than that in IM patients with liver injury(P<0.0001).The percentage of CD56^(+)CD16^(+)NK cells in IM patients with liver injury(62.03+8.78)%and IM patients without liver injury(44.74±13.03)%were higher than that in controls(40.74+10.15)%(P<0.05).CD56^(+)CD16^(+)NK cell frequency in IM patients with liver injury also was higher than that in IM patients with liver injury(P<0.0001).There was no statistical difference of CD56~CD16^(+)NK cell proportion among three groups(P=0.427).Plasma IL-15 level in IM patients with liver injury(309.1±68.00)pg/ml were higher than that in IM patients without liver injury(269.6+53.57)pg/ml and controls(257.4±73.93)pg/ml(P<0.05).NK cells induced target cell death through different recepto

关 键 词：EB病毒 传染性单核细胞增多症 肝损伤 自然杀伤细胞 

分 类 号：R512.7[医药卫生—内科学]