Liver-Resident NK Cells Control Antiviral Activity of Hepatic T Cells via the PD-1-PD-L1 Axis
Open accessAbstract
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.
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During chronic infection with lymphocytic choriomeningitis virus, NK cells up-regulated PD-L1, thereby inhibiting the function of virus-specific CTLs.
“By contrast, during chronic infection with lymphocytic choriomeningitis virus (LCMV), a rodent-borne virus, NK cells up-regulated PD-L1 thereby inhibiting the function of virus-specific CTLs(191).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [191]
Cites
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BackgroundCXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver
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The liver as a central "hub" of the immune system: pathophysiological implications
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- Authors
- Zhou, J., Peng, H., Li, K., Qu, K., Wang, B., Wu, Y., Ye, L., Dong, Z., Wei, H., Sun, R., & Tian, Z.
- Affiliations
- University of Science and Technology of China (CN)
- Army Medical University (CN)
- Tsinghua University (CN)
- Corresponding author
- Peng, Hui
- Tian, Zhigang
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 50
- Issue
- 2
- Pages
- 403-417.e4
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2912678610
- Cited by
- 157
- References
- 3
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 24 · 2023: 16 · 2022: 23 · 2021: 28 · 2020: 28 · 2019: 18
- FWCI
- 9.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Chinese Academy of Sciences (XDB29030000)
- National Natural Science Foundation of China (91542114, 91642105, 81571522, 81788101, 81761128013, 91542000)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
- Keywords
- natural killer cells, PD-1/PD-L1 axis, antiviral immunity, lymphocytic choriomeningitis virus, adenovirus infection, viral clearance, immune tolerance, T cell suppression
- MeSH terms
- Animals, Killer Cells, Natural, Liver, Lymphocytic Choriomeningitis, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Signal Transduction, Mice, Knockout, Hepatocytes, Transcriptome, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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