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

Area of Science:

• Immunology
• Hepatology
• Cellular Biology

Background:

• Programmed cell death-1 (PD-1) is crucial for T lymphocyte regulation, but its precise mechanisms remain unclear.
• CD8+ T lymphocyte dysfunction is a hallmark of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).

Purpose of the Study:

• To investigate the role of PD-1 in CD8+ T lymphocyte dysfunction within the context of HBV-ACLF.
• To explore the potential link between PD-1 signaling and metabolic alterations in CD8+ T cells during HBV-ACLF.

Main Methods:

• Comparative analysis of CD8+ T lymphocyte numbers, function, and PD-1/glucose transporter-1 (Glut1) expression in HBV-ACLF patients versus healthy controls (HCs).
• In vitro study involving cultured CD8+ T lymphocytes from HCs and ACLF patients, with or without PD-1/PD-L1 pathway activation.
• Assessment of glycogen uptake, cellular functions, and expression of key glycolytic enzymes (Glut1, hexokinase-2, pyruvate kinase) in CD8+ T cells.

Main Results:

• Patients with HBV-ACLF exhibited lower CD8+ T lymphocyte counts and increased PD-1 expression compared to HCs.
• CD8+ T lymphocytes from HBV-ACLF patients showed impaired function and reduced Glut1 expression.
• In vitro PD-1/PD-L1 activation in ACLF CD8+ T cells led to decreased glycogen uptake and reduced expression of glycolytic enzymes, further impairing T cell function.

Conclusions:

• CD8+ T lymphocyte dysfunction is evident in HBV-ACLF patients.
• PD-1-mediated T lymphocyte dysfunction in HBV-ACLF may be associated with the inhibition of glycolysis.