Mucosal‐associated invariant T‐cells are severely reduced and exhausted in humans with chronic HBV infection

Abstract

Mucosal-associated invariant T (MAIT) cells, defined as CD161 + TCR Vα7.2 + CD3+ T-cells, are a subset of αβ T-cells that possess both innate-and effector-like qualities. 1,2 They are preferentially located in the gut lamina propria and liver 3 and comprise ~1%-10% of the circulating CD3 + T-cells and ~20%-50% of the intrahepatic T-cells in healthy adults. 4,5 MAIT cells play an important role in innate defence against bacterial infections and can be activated by MR1-presented bacterial ligands or by IL-12 and IL-18. 6,7 Chronic hepatitis B virus (CHBV) infection is a noncytopathic infection of host hepatocytes that affects over 240 million people

Functional inactivation of pulmonary MAIT cells following 5-OP-RU treatment of non-human primates

“…Previous studies have documented defects in MAIT cell function during infection, cancer and sepsis (29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Our data showing MAIT cell functional defects directly resulting from TCR stimulation indicates that part of the MAIT dysfunction observed in these settings may result from increased MAIT antigen stimulation, rather than disease-related bystander processes.…”

“…Interestingly, the defect in cytokine production after 5-OP-RU treatment was only observed when the cells were restimulated with 5-OP-RU, and the cells displayed equivalent higher cytokine production as controls upon PMA/ionomycin restimulation, indicating that the defect relates to signaling through the TCR. It is possible that multiple co-inhibitory receptors cooperate in MAIT cell inactivation, as MAIT cells have been shown to express several different immune checkpoint molecules (31, 33, 34, 40, 41).…”

Leveraging Public Single-Cell and Bulk Transcriptomic Datasets to Delineate MAIT Cell Roles and Phenotypic Characteristics in Human Malignancies

“…Another difference between these two studies is the rate of hepatitis B virus (HBV) infection among HCC patients, which was low in the TCGA cohort ( 89 ) and highly prevalent in the cohorts studied by Duan et al ( 20 ). Chronic HBV infection is the most common risk factor for HCC ( 90 ), and has recently been associated with peripheral blood MAIT cell activation and exhaustion although its impact on hepatic MAIT cells is less clear ( 91 – 93 ). Our pathway enrichment analysis in the HCC scRNA-seq dataset generated by Zheng et al, in which all patients were HBV-positive unlike in the TCGA cohort, revealed the upregulation of antiviral gene modules in tumor-infiltrating MAIT cells.…”

Functional inactivation of pulmonary MAIT cells following 5-OP-RU treatment of non-human primates

“…It is possible that multiple co-inhibitory receptors cooperate in MAIT cell inactivation, as MAIT cells have been shown to express several different immune checkpoint molecules. 32 , 34 , 35 , 41 , 42 …”