NK cell Activation during Acute Hepatitis C Virus Infection (45.18)

Abstract

Abstract Genetic studies have implicated the inhibitory natural killer (NK) cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand in resolution of hepatitis C virus (HCV) infection but a functional correlation was not established. To examine the role of NK cells during acute HCV, we have analyzed longitudinally the phenotype and function of NK cells from a cohort of patients following HCV exposure. Three groups with different infectious outcome were identified: spontaneous resolvers (SR), chronic evolution (C) and exposed un-infected (EU) (n=10 in each group). We have observed increased NK cell cytotoxicity (%CD107a+) in all groups suggesting NK cell activation following exposure but no correlation was established with infectious outcome. Nevertheless, we observed decreased expression of KIR2DL1, associated with highest NK cell inhibition, in SR. Furthermore, the highest IFN-γ production was observed in KIR2DL3+ NK cells, the least inhibited population, in all groups. Our results suggest that NK cell direct cytotoxicity might not be implicated in HCV clearance but that less NK cell inhibition is more frequent in SR patients. These results confirm the important role of host genetic background in NK cell function and provides the first demonstration of such a functional correlation in an in vivo infection setting. Research support: The Dana Foundation, CIHR, FRSQ, NCRTP-HepC