Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis

Abstract

The tolerogenic microenvironment of the liver is associated with impaired hepatic Tcell function. Here, weexamined the contribution of liver-resident naturalkiller (LrNK) cells, a prominent hepatic NK cell compartment, to Tcell antiviral responses in the liver. The number of virus-specific Tcells increased in LrNK-cell-deficient mice during both acute and chronic lymphocytic choriomeningitis virus infection. Upon infection with adenovirus, hepatic Tcells from these mice produced more cytokines, which was accompanied by reduced viral loads. Transfer of LrNK cells into LrNK-cell-deficient or wild-type mice inhibited hepatic Tcell function, resulting in impaired viral clearance, whereas transfer of conventional NK cells promoted Tcell antiviral responses. LrNK-cell-mediated inhibition of Tcell function was dependent on the PD-1-PD-L1 axis. Our findings reveal a role forLrNK cells in the regulation of Tcell immunity and provide insight into the mechanisms of immune tolerance in the liver.