Hepatitis B Virus--Specific and Global T-Cell Dysfunction in Chronic Hepatitis B.

Area of Science:

• Immunology
• Virology
• Hepatology

Background:

• T cells are crucial in managing viral infections.
• Chronic hepatitis B (CHB) is a persistent viral infection with complex immune responses.
• Understanding T-cell dynamics in CHB is vital for defining disease stages and progression.

Purpose of the Study:

• To investigate if T-cell effector and regulatory responses can distinguish clinical stages of CHB.
• To analyze T-cell responses to hepatitis B virus (HBV) peptides and other antigens in CHB patients.
• To explore the role of regulatory T cells and immune checkpoint molecules in CHB pathogenesis.

Main Methods:

• Enrolled 200 adults with CHB and 20 controls.
• Analyzed peripheral blood lymphocytes for T-cell proliferation and cytokine production (interferon gamma, interleukin 10) in response to HBV peptides.
• Assessed T-cell expression of FOXP3, programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) via flow cytometry.

Main Results:

• CHB patients exhibited weak T-cell responses to HBV and increased regulatory T cells (FOXP3(+)CD127(-)) and immune checkpoint expression (PD-1, CTLA-4).
• T-cell measures did not clearly differentiate CHB clinical phenotypes, though HBV core-specific responses were weaker in hepatitis B e antigen (HBeAg)(+) patients.
• In vitro blockade of PD-1 or CTLA-4 partially restored T-cell responses, with a weaker effect in HBeAg(+) individuals.

Conclusions:

• HBV infection is associated with virus-specific and global T-cell dysfunction, influenced by regulatory mechanisms like HBeAg.
• Distinct T-cell immune signatures for CHB clinical phenotypes were not identified.
• Additional T-cell-independent or regulatory mechanisms likely contribute to CHB pathogenesis, warranting further investigation.