Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Institue of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China; Institue of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China.
Immunity. 2019 Feb 19;50(2):403-417.e4. doi: 10.1016/j.immuni.2018.12.024. Epub 2019 Jan 29.
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.
肝脏的耐受微环境与肝 T 细胞功能受损有关。在这里，我们研究了肝固有自然杀伤（LrNK）细胞——肝 NK 细胞的主要组成部分——对肝脏中 T 细胞抗病毒反应的贡献。在急性和慢性淋巴细胞性脉络丛脑膜炎病毒感染期间，LrNK 细胞缺陷小鼠的病毒特异性 T 细胞数量增加。在感染腺病毒时，这些小鼠的肝 T 细胞产生了更多的细胞因子，同时病毒载量降低。将 LrNK 细胞转移到 LrNK 细胞缺陷型或野生型小鼠中会抑制肝 T 细胞功能，导致病毒清除受损，而转移常规 NK 细胞则促进 T 细胞抗病毒反应。LrNK 细胞介导的 T 细胞功能抑制依赖于 PD-1-PD-L1 轴。我们的研究结果揭示了 LrNK 细胞在调节 T 细胞免疫中的作用，并深入了解了肝脏免疫耐受的机制。
