Changes in natural killer cell frequency,function,and receptor expression in peripheral blood of patients with hepatitis B cirrhosis

Objective To investigate the changes in natural killer(NK) cell frequency,function,and receptor expression in the peripheral blood of patients with hepatitis B cirrhosis.Methods A total of 34 patients with hepatitis B cirrhosis who were admitted to 302 Hospital of PLA from June 2013 to December 2014 were enrolled as the cirrhosis group,and 30 healthy blood donors were enrolled as the healthy control group.Flow cytometry was used to measure NK cell frequency and the expression of CD158 a,CD158b,NKG2 D,NKP30,NKP44,and NKP46 receptors in peripheral blood.Interleukin- 12(IL- 12) was used to stimulate peripheral blood mononucleated cells,and flow cytometry was used to measure the ability of NK cells to secrete interferon- γ(IFNγ) and tumor necrosis factor- α(TNFα) and analyze the killing efficiency of NK cells for K562 cells.NK cell frequency,receptor expression,and function were compared between the two groups.The t- test was used for comparison of normally distributed data between groups,and the Mann- Whitney U rank sum test was used for comparison of abnormally distributed data between groups.Results Compared with the healthy control group,the cirrhosis group had a significantly lower CD56 dimNK cell frequency(Z =- 2.309,P < 0.05) and a significantly higher CD56 brightNK cell frequency(Z = 2.395,P < 0.05).The cirrhosis group had significantly higher expression rates of NKP44 and NKP46(the activating receptors of CD56 dimNK cells) than the healthy control group(Z = 2.834 and 3.404,both P < 0.05).The cirrhosis group also had significantly higher expression rates of NKP30,NKP44,and NKP46(the receptors of CD56 brightNK cells) than the healthy control group(Z = 3.518,4.003,and 4.480,all P <0.05).After IL- 12 stimulation,compared with the healthy control group,the cirrhosis group had significantly lower expression rates of TNFα in CD56 dimNK cells and IFNγ in CD56 brightNK cells(Z =- 3.510 and- 4.301,both P < 0.05).With effector- target ratios of 3∶ 1,10∶ 1,and 30∶ 1,the cirrhosis group had significantly lower proportions of K562 cells killed by NK cells than the healthy control group(Z =- 2.355,- 2.523,and- 2.523,all P < 0.05).Conclusion The patients with liver cirrhosis experience a reduced NK cell function,which may be related to reduced frequency of CD56 dimNK cells and secretion of cytokines,but may not be related to receptor expression.