The tolerogenic microenvironment of the liver is associated with impaired hepatic T cell function. Here, we examined the contribution of liver-resident natural killer (LrNK) cells, a prominent hepatic NK cell compartment, to T cell antiviral responses in the liver. The number of virus-specific T cells increased in LrNK-cell-deficient mice during both acute and chronic lymphocytic choriomeningitis virus infection. Upon infection with adenovirus, hepatic T cells 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 T cell function, resulting in impaired viral clearance, whereas transfer of conventional NK cells promoted T cell antiviral responses. LrNK-cell-mediated inhibition of T cell function was dependent on the PD-1-PD-L1 axis. Our findings reveal a role for LrNK cells in the regulation of T cell immunity and provide insight into the mechanisms of immune tolerance in the liver.

肝脏的致耐受性微环境与肝T细胞功能受损有关。在这里，我们检查了肝脏驻留自然杀手（LrNK）细胞（肝脏NK细胞的显着区隔）对肝脏T细胞抗病毒反应的贡献。在急性和慢性淋巴细胞性脉络膜脑膜炎病毒感染期间，LrNK细胞缺陷型小鼠中病毒特异性T细胞的数量均增加。感染腺病毒后，这些小鼠的肝T细胞产生更多的细胞因子，并伴有病毒载量减少。LrNK细胞转移到LrNK细胞缺陷或野生型小鼠转移抑制肝T细胞功能，导致病毒清除受损，而常规NK细胞转移促进T细胞抗病毒反应。LrNK细胞介导的T细胞功能抑制取决于PD-1-PD-L1轴。