Introduction Hepatitis C virus (HCV) infection results in chronic infection in the majority of subjects, indicating viral immunoevasion strategies. Treatment with interferon alpha (IFNα) stimulates the immune system but the role of NK cells remains unclear.
Methods Intra-hepatic NK cells were obtained from 20 HCV infected donors prior to treatment and 16 non-viral chronic liver disease (CLD) patients along with paired peripheral blood samples. NK phenotype (CD16, NKp30, NKp46, NKG2D and NKG2A) and functional profile (Ki67, CD107a, IFN-γ and Granzyme B) was assessed by flow cytometry. In a separate cohort of 8 HCV patients, who had completed treatment, rate of viral clearance was calculated and pre-treatment peripheral blood NK phenotype and CD107a expression in response to increasing stimulation was measured. At low-level stimulation peripheral blood mononuclear cells (PBMCs) were incubated overnight with 50 u/ml IFNα and exposed to Huh7. Five target cells and at maximal stimulation PBMCs were incubated with 1000 u/ml IFNα and K562 target cells.
Results Intrahepatic vs peripheral blood NK cells demonstrated significantly less expression of CD16 (p NKG2D and NKp30 expression was increased in PBMCs of HCV patients with a more striking down regulation of NKG2D in the liver (p. There was no difference in NKp46 or NKG2A expression between the intrahepatic and peripheral NK cells in either cohort. However, the necroinflammatory score of HCV subjects correlated with NKp46 expression (p=0.003), CD107a expression (p=0.05) and IFN-γ (p=0.05). In the treated cohort, an increased rate of viral clearance correlated with an increased ability of the NK cells to upregulate CD107a (r2=0.5 p<0.05) to increasing stimulation, which was inversely correlated with expression of NKp46 (r2=0.85 p=0.001) at baseline.
Conclusion Intrahepatic NK cells acquire a distinct phenotype and functional profile. NK phenotype and function correlates with necroinflammatory score in HCV infection. The NK cells ability to be activated with IFNα is associated with rapid control of the virus.
Competing interests None declared.
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