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

作　　者：Chi-Chang Sung Jau-Hau Horng Shih-Hong Siao I-Tsu Chyuan Hwei-Fang Tsai Pei-Jer Chen Ping-Ning Hsu 

机构地区：[1]Graduate Institute of Immunology,College of Medicine,National Taiwan University,Taipei,China [2]Graduate Institute of Microbiology,College of Medicine,National Taiwan University,Taipei,China [3]Department of Internal Medicine,Cathay General Hospital,Taipei,China [4]School of Medicine,College of Medicine,Fu Jen Catholic University,New Taipei City,China [5]Department of Internal Medicine,Taipei Medical University Shuang Ho Hospital,Taipei,China [6]Graduate Institute of Clinical Medicine,College of Medicine,National Taiwan University,Taipei,China [7]Department of Internal Medicine,National Taiwan University Hospital,Taipei,China

出　　处：《Cellular & Molecular Immunology》2021年第7期1772-1782,共11页中国免疫学杂志（英文版）

基　　金：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).

摘　　要：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.

关 键 词：asialo GM-1 liver-resident CD8 T cells HBV clearance 

分 类 号：R512.62[医药卫生—内科学]