PD-1 Involvement in Peripheral Blood CD8 T Lymphocyte Dysfunction in Patients with Acute-on-chronic Liver Failure

Overview

Journal J Clin Transl Hepatol

Specialty Gastroenterology

Date 2021 Jul 5

PMID 34221914

Citations 2

Authors

Xiaoshuang Zhou

Yidong Li

Yaqiu Ji

Tian Liu

Ninghui Zhao

Jiefeng He

Jia Yao

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Programmed cell death-1 (PD-1) plays an important role in downregulating T lymphocytes but the mechanisms are still poorly understood. This study aimed to explore the role of PD-1 in CD8 T lymphocyte dysfunction in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Methods: Thirty patients with HBV-ACLF and 30 healthy controls (HCs) were recruited. The differences in the numbers and functions of CD8 T lymphocytes, PD-1 and glucose transporter-1 (Glut1) expression from the peripheral blood of patients with HBV-ACLF and HCs were analyzed. , the CD8 T lymphocytes from HCs were cultured (HC group) and the CD8 T lymphocytes from ACLF patients were cultured with PD-L1-IgG (ACLF+PD-1 group) or IgG (ACLF group). The numbers and functions of CD8 T lymphocytes, PD-1 expression, glycogen uptake capacity, and Glut1, hexokinase-2 (HK2), and pyruvate kinase (PKM2) expression were analyzed among the HC group, ACLF group and ACLF+ PD-1group.

Results: The absolute numbers of CD8 T lymphocytes in the peripheral blood from patients with HBV-ACLF were lower than in the HCs (<0.001). The expression of PD-1 in peripheral blood CD8 T lymphocytes was lower in HCs than in patients with HBV-ACLF (=0.021). Compared with HCs, PD-1 expression was increased (=0.021) and Glut1 expression was decreased (=0.016) in CD8 T lymphocytes from the HBV-ACLF group. , glycogen uptake and functions of ACLF CD8 T lymphocytes were significantly lower than that in HCs (=0.017; all <0.001). When PD-1/PD-L1 was activated, the glycogen uptake rate and expression levels of Glut1, HK2, and PKM2 showed a decreasing trend (ACLF+PD-1 group compared to ACLF group , all <0.05). The functions of CD8 T lymphocytes in the ACLF+PD-1 group [using biomarkers of Ki67, CD69, IL-2, interferon-gamma, and tumor necrosis factor-alpha- were lower than in the ACLF group (all <0.05).

Conclusions: CD8 T lymphocyte dysfunction is observed in patients with HBV-ACLF. PD-1-induced T lymphocyte dysfunction might involve glycolysis inhibition.

Citing Articles

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