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

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.

Keywords: PD-L1; antiviral responses; conventional NK cells; hepatic T cells; liver-resident NK cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / immunology*
  • B7-H1 Antigen / metabolism
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Liver / immunology*
  • Liver / metabolism
  • Liver / virology
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / metabolism
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Lymphocytic choriomeningitis virus / physiology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / immunology*
  • Programmed Cell Death 1 Receptor / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / virology
  • Transcriptome / genetics
  • Transcriptome / immunology


  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Programmed Cell Death 1 Receptor