Increased degranulation of natural killer cells during acute HCV correlates with the magnitude of virus-specific T cell responses

Background & Aims: Natural killer (NK) cells provide early defense against viral infections by killing infected cells and producing cytokines that inhibit viral replication. NK cells also interact with dendritic cells (DCs) and this reciprocal interaction regulates both innate and adaptive immunity. Genetic studies have suggested that NK cell activity is a determinant of HCV infectious outcome but a functional correlation has not been established. We hypothesized that increased NK cell activity during acute HCV infection correlates with spontaneous viral clearance. Methods: We used multiparametric flow cytometry to monitor longitudinally the phenotype and the activity of NK cells in a cohort of intravenous drug users following HCV exposure. Three groups were studied: acute HCV with chronic evolution (n = 13), acute resolving HCV (n = 11), and exposed un-infected individuals (n = 10). We examined the expression of several NK cell-activating and -inhibiting receptors, IFN-gamma production and CD107a degranulation upon stimulation, and the kinetics of NK cell responses relative to T cell responses. Results: We observed decreased expression of the inhibitory NKG2A receptor in NK cells following spontaneous HCV clearance. In addition, we observed increased NK cell degranulation during acute HCV irrespective of infectious outcome. NIC cell peak responses preceded or coincided with peak T cell responses. Furthermore, NIC cell degranulation correlated with the magnitude of HCV-specific T cells. Conclusions: Our results demonstrate that NK cells are activated during acute HCV regardless of infection outcome and may play an indirect role through induction and priming of T cell responses. (C) 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.