Introduction Hepatitis C virus (HCV) infection is the leading cause for liver transplantation (LT) and recurrence post LT is universal. The role of NK cells in this context is poorly understood, in relation to both alloreactivity and antiviral response. This study investigates whether there are differences in NK cell activation between individuals transplanted for HCV and those transplanted for non-HCV indications.
Methods Whole blood was collected from 28 liver transplant patients (18 HCV, 10 non-HCV) and 16 controls. The transplant patients were all on calcineurin inhibitor-based immunosuppression. NK cells from the peripheral blood were analysed for expression of the cell surface inhibitory receptors CD158a/b (killer cell immunoglobulin-like receptors (KIR) specific for HLA-C), and the activating receptors NKp30, NKp46 and NKG2D. Following overnight incubation with IL-15 NK cell function was assessed using a flow cytometry-based killing assay.
Results Compared with controls, there was significantly reduced expression of NKp30 and NKp46 in non-HCV LT patients (p<0.001 for both, Student t test), but no reduction in activating receptor expression in individuals transplanted for HCV. There was no segregation of activating receptor expression with expression of specific KIR. The functional assays correlated with the phenotyping data, with significantly reduced NK cell killing of target cells in non-HCV LT patients compared with controls and with HCV LT patients (p=0.02 and 0.01 respectively, Student t test).
Conclusion The recipient NK cell response to liver transplantation is altered in individuals with HCV infection. In the non-HCV setting, we have demonstrated down-regulation of NK activation which may facilitate tolerance. However in the presence of HCV, NK cell function remains intact. We hypothesise that this phenomenon contributes to allograft inflammation and the poorer outcomes observed in LT for HCV.
Competing interests None declared.