Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Saturday, 10 / 16 / 2021

Abstract

ORIGINAL ARTICLE

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

Xiaoshuang Zhou1, Yidong Li2, Yaqiu Ji2, Tian Liu2, Ninghui Zhao2,*, Jiefeng He3,*and Jia Yao2,4,*

1  Department of Nephrology, Shanxi Provincial People’s Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
2  Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
3  Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi, China
4  Institute of Liver Disease and Organ Transplantation, Shanxi Medical University, Taiyuan, Shanxi, China
*Correspondence to:Jia Yao and Ninghui Zhao, Department of Gastroenterology, Shanxi Baiqiuen Hospital, Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, Shanxi 030001, China. ORCID:  https://orcid.org/0000-0003-2210-7717 (JY),https://orcid.org/0000-0002-9715-9303(NZ). Tel/Fax: +86-199-3491-1619, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. (JY) and This email address is being protected from spambots. You need JavaScript enabled to view it. (NZ); Jiefeng He, Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, China. ORCID:  https://orcid.org/0000-0003-2958-0232.E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(3):283-290 DOI: 10.14218/JCTH.2020.00142
Received: November 30, 2020 Accepted: March 7, 2021 Published online: March 31, 2021

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.In vitro, 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 (p<0.001). The expression of PD-1 in peripheral blood CD8+ T lymphocytes was lower in HCs than in patients with HBV-ACLF (p=0.021). Compared with HCs, PD-1 expression was increased (p=0.021) and Glut1 expression was decreased (p=0.016) in CD8+ T lymphocytes from the HBV-ACLF group. In vitro, glycogen uptake and functions of ACLF CD8+ T lymphocytes were significantly lower than that in HCs (p=0.017; all p<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 p<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 p<0.05).

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

Keywords

Acute and chronic liver failure, Programmed cell death 1, Immune function, Glycolysis, Glut1

Journal of Clinical and Translational Hepatology 2021 vol. 9, 283-290  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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