Restoration of CD3+CD56+ NKT‐like cell function by TIGIT blockade in inactive carrier and immune tolerant patients of chronic hepatitis B virus infection

Author:

Yu Xiaojing1,Zheng Yuanling1,Huang Ruoyu1,Dai Xiaoran1,Kang Guijie23,Wang Xuefu23,Yan Guoxiu4,Ding Biran1,Zheng Meijuan1,Xu Yuanhong1,Zong Lu1ORCID

Affiliation:

1. Department of Clinical Laboratory The First Affiliated Hospital of Anhui Medical University Hefei China

2. Inflammation and Immune‐Mediated Diseases Laboratory of Anhui Province Anhui Medical University Hefei China

3. Department of Basic and Clinical Pharmacy School of Pharmacy Anhui Medical University Hefei China

4. Department of Clinical Laboratory Anhui Provincial Maternity and Child Health Hospital Hefei China

Abstract

AbstractChronic hepatitis B (CHB) virus infection, which can be divided into immune‐tolerant (IT), immune‐active (IA), inactive carrier (IC) phases, and HBeAg‐negative hepatitis (ENEG), can induce liver cirrhosis and eventually hepatocellular carcinoma (HCC). CD3+CD56+ NKT‐like cells play an important role in antiviral immune response. However, the mechanism of NKT‐like cells to mediate immune tolerance remains largely elusive. In this study, we observed circulating NKT‐like cells from IC and IT CHB patients were phenotypically and functionally impaired, manifested by increased expression of inhibitory receptor TIGIT and decreased capacity of secreting antiviral cytokines. Besides, TIGIT+ NKT‐like cells of IC and IT CHB patients expressed lower levels of cytotoxic cytokines than the TIGIT subset. Furthermore, increased expression of CD155, the ligand of TIGIT, on plasmacytoid dendritic cells (pDCs) was detected in IC and IT CHB patients. Importantly, the co‐culture of NKT‐like cells and pDCs showed that NKT‐like cells restored their antiviral ability after TIGIT blockade upon HBV peptide stimulation in IC and IT CHB patients. In conclusion, our findings suggest that the TIGIT pathway may mediate immune tolerance in IT CHB patients and lead to functional impairment in IC patients, indicating that TIGIT may be a potential therapeutic checkpoint for immunotherapy of CHB patients.

Funder

Scientific Research Foundation of Education Department of Anhui Province of China

Natural Science Foundation of Anhui Province

National Natural Science Foundation of China

Publisher

Wiley

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