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

Abstract

To investigate the changes of subpopulation and function of natural killer (NK) cells in adult patients with infectious mononucleosis related liver injury. 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 enzyme 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 t test were used for statistical analysis. 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 receptors upon activation, the ratio of CD107a-positive cells in NK cells of IM patients with liver injury was higher than that in IM patients without liver injury and controls (P<0.05), while CD16 MFI in NK cells in IM patients with liver injury was lower than that in IM patients without liver injury and controls (P<0.05). The percentage of CD107a positive cells in NK cells was significantly reduced in response to anti-IL-15 neutralizing antibody stimulation in IM patients with liver injury (P<0.05). IM patients with liver injury presented imbalance of NK cell subpopulation and enhanced NK cell function. The elevation of IL-15 might contribute to promote NK cell cytotoxicity in IM patients with liver injury.