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Asialo GM1-positive liver-resident CD8 T cells that express CD44 and LFA-1 are essential for immune clearance of hepatitis B virus

Cellular & Molecular Immunology volume 18, pages 1772–1782 (2021)Cite this article

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Abstract

Persistent hepatitis B virus (HBV) infection results in chronic liver diseases that may progress to chronic hepatitis, liver cirrhosis, and subsequent hepatocellular carcinoma. Previous studies demonstrated that adaptive immunity, in particular CD8 T cells, is critical in HBV elimination. Recent studies have revealed a distinct tissue-localized T cell lineage, tissue-resident memory (TRM) cells, that is crucial for protective immunity in peripheral tissues. In this study, we showed that treatment with an anti-asialo GM1 (ASGM1) antibody (Ab), which depletes NK cells, led to impairment of HBV clearance in a mouse animal model. Unexpectedly, the ability to clear HBV was not significantly impaired in NFIL3 KO mice, which are deficient in NK cells, implying that other non-NK ASGM1-positive immune cells mediate HBV clearance. We isolated intrahepatic ASGM1-positive cells from NFIL3 KO mice and analyzed the immune phenotype of these cells. Our results demonstrated a distinct population of CD44+ LFA-1hi CD8 T cells that were the major intrahepatic ASGM1-positive immune cells in NFIL3 KO mice. Importantly, transcriptome analysis revealed that these ASGM1-positive CD8 T cells had distinct gene profiles and shared a similar core gene signature with TRM cells. In addition to both transcriptional and phenotypic liver residency characteristics, ASGM1-positive CD8 T cells were able to home to and be retained in the liver after adoptive transfer. Taken together, our study results indicate that these ASGM1-positive liver-resident CD8 T cells are the major effector immune cells mediating anti-HBV immunity.

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Acknowledgements

This work was supported by grants from the Ministry of Science and Technology (MOST 105-2320-B-038-065, MOST 106-2320-B-038-0193, MOST 107-2321-B-002-003, and MOST 108-2320-B-002-036-MY3).

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Authors and Affiliations

  1. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, China

    Chi-Chang Sung, Shih-Hong Siao & Ping-Ning Hsu

  2. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, China

    Jau-Hau Horng

  3. Department of Internal Medicine, Cathay General Hospital, Taipei, China

    I-Tsu Chyuan

  4. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, China

    I-Tsu Chyuan

  5. Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, Taipei, China

    Hwei-Fang Tsai

  6. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, China

    Pei-Jer Chen

  7. Department of Internal Medicine, National Taiwan University Hospital, Taipei, China

    Ping-Ning Hsu

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  1. Chi-Chang Sung
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Correspondence to Ping-Ning Hsu.

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Sung, CC., Horng, JH., Siao, SH. et al. Asialo GM1-positive liver-resident CD8 T cells that express CD44 and LFA-1 are essential for immune clearance of hepatitis B virus. Cell Mol Immunol 18, 1772–1782 (2021). https://doi.org/10.1038/s41423-020-0376-0

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