Study On The Relationship Between NK Cells,Treg And Cytokines In Patients With Chronic HBV Infection

Objective : To investigate the relationship between IFN-γ secreted by NK cells and Treg and IL-10 in peripheral blood of patients with chronic HBV infection and the progressive diseases such as LC and HCC.Methods: 146 patients with chronic HBV were collected,including 57 patients with chronic hepatitis B(CHB),40 patients with HBV-related LC and 22 patients with HBV-related HCC.Twenty-seven healthy persons were selected for physical examination in the same period.The percentage of Treg,cytokines(IL-10,IFN-γ,IL-2,IL-4,TNF and IL-5)in peripheral blood,the proportion of NK cells and the percentage of IFN-γ produced by NK cells were detected by flow cytometry.Serum ALT and AST levels were detected by automatic biochemical analyzer.LSD test,Mann-Whitney U test and Spearman correlation test were used for statistical analysis.Results: The percentages of Treg cells in peripheral blood and the level of IL-10 in serum of patients with CHB,LC and HCC were significantly higher than those of HC group,and the absolute value of Tregs in peripheral blood of patients with CHB and HCC was also significantly higher than that of HC group(P<0.05).Treg was positively correlated with IL-10 in CHB,LC and HCC groups(P<0.01,r=0.564;P< 0.01,r=0.426;P<0.05,r=0.476).In addition,the absolute number of NK cells,the percentage of IFN-γ+ NK cells and the content of IFN-γ in serum in CHB,LC and HCC groups were significantly lower than those in HC group(P< 0.01).Meanwhile,the proportion of IFN-γ+NK cells in CHB patients was negatively correlated with Treg cells and serum IL-10 levels(P<0.05,r=-0.618;P<0.05,r=-0.635),and serum IFN-γ levels were negatively correlated with Treg(P< 0.01,r=-0.342);in LC patients,the absolute number of NK cells in peripheral blood was negatively correlated with the proportion of Treg cells(P<0.05,r=-0.317),the proportion of IFN-γ+NK cells was negatively correlated with the level of IL-10 in serum(P<0.05,r=-0.514);the proportion of IFN-γ+NK cells in HCC patients was negatively correlated with the proportion of Tregs and the level of IL-10 in serum(P<0.01,r=-0.676;P<0.01,r=-0.615).Conclusion: The proportion of IFN-γ+NK cells in peripheral blood of CHB patients and their progressive diseases,such as LC and HCC,is negatively correlated with the proportion of Treg cells and the serum levels of IL-10,suggesting that the involvement of Treg and IL-10 in inhibiting IFN-γ+NK cells may be one of the important factors involved in chronic HBV infection and its progression,thus reversing the immune tolerance induced by Treg and IL-10.Therefore,reversing the immune tolerance induced by Treg and IL-10 will effectively improve NK cell functions which result in the control of progress of CHB.