Mucosal-associated Invariant T-cells Are Severely Reduced and Exhausted in Humans With Chronic HBV Infection
Wenyong Huang 1 2 3 , Wenjing He 1 2 3 , Xiaomin Shi 1 2 3 , Qianyu Ye 1 2 3 , Xiaoshun He 1 2 3 , Dou Lang 1 2 3 , Yifang Gao 1 2 3
Affiliations
Affiliations
1
Organ Transplantation Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
2
Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China.
3
Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
PMID: 32510704 DOI: 10.1111/jvh.13341
Abstract
Chronic hepatitis B virus (CHBV) infection is a major cause of liver diseases. Mucosal-associated invariant T (MAIT) cells are important for antiviral immunity in the liver, but the distinction between intrasinusoidal and peripheral MAIT cells in patients with CHBV infections remains unclear. PBMCs were obtained from patients with CHBV infections (n=29) and age-matched controls (n=46). Liver-associated mononuclear cells (LMCs) were collected from healthy donors (n=29) and explanted livers (n=19) from patients and used for phenotypic, functional and TCR diversity analyses. The percentages of both peripheral and intrasinusoidal MAIT cells were significantly reduced in the CHBV infection group compared to the control group. Peripheral MAIT cells from CHBV-infected patients expressed higher levels of HLA-DR, CD69, CD38, and PD-1 than those of controls. We also confirmed that peripheral MAIT cells in HBV patients had elevated expression T-cell exhaustion genes. Except for a difference in the level of PD-1, no differences were observed between the liver MAIT cells of the two groups. The production of IFN-α in peripheral MAIT cells of CHBV infection patients was lower than in control patients, but no such difference was observed in liver MAIT cells. Additionally, a distinct TCR signature was found in CHBV patients. Hence we found distinct activities and functions in liver and peripheral MAIT cells of patients with CHBV infections.