1. Asialo GM1-positive liver-resident CD8 T cells that express CD44 and LFA-1 are essential for immune clearance of hepatitis B virus
- Author
-
Jau-Hau Horng, Hwei-Fang Tsai, Pei-Jer Chen, Chi-Chang Sung, I-Tsu Chyuan, Shih-Hong Siao, and Ping-Ning Hsu
- Subjects
0301 basic medicine ,Hepatitis B virus ,Adoptive cell transfer ,T cell ,Immunology ,G(M1) Ganglioside ,CD8-Positive T-Lymphocytes ,Biology ,medicine.disease_cause ,Article ,Mice ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Immune system ,Immunity ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,Hepatitis B ,Acquired immune system ,Lymphocyte Function-Associated Antigen-1 ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Liver ,biology.protein ,Antibody ,030215 immunology - 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-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.
- Published
- 2020