Journal
CELLULAR & MOLECULAR IMMUNOLOGY
Volume 18, Issue 7, Pages 1772-1782Publisher
CHIN SOCIETY IMMUNOLOGY
DOI: 10.1038/s41423-020-0376-0
Keywords
asialo GM-1; liver-resident CD8 T cells; HBV clearance
Categories
Funding
- Ministry of Science and Technology [MOST 105-2320-B-038-065, MOST 106-2320-B-038-0193, MOST 107-2321-B-002-003, MOST 108-2320-B-002-036-MY3]
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This study identified ASGM1-positive liver-resident CD8 T cells as the major effector immune cells that mediate anti-HBV immunity, working in coordination with TRM cells and other immune cells to clear HBV.
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-1(hi) 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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