Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8⁺ T cell quality

Area of Science:

• Immunology
• Hepatology
• Virology

Background:

• Chronic hepatitis B (CHB) is characterized by persistent hepatitis B surface antigen (HBsAg) despite treatment.
• The role of CD8+ T cell responses in managing viral replication and reducing HBsAg levels in CHB patients on nucleos(t)ide analog (NUC) therapy is not fully understood.

Purpose of the Study:

• To investigate the characteristics of activated CD8+ T cells and HBV-specific CD8+ T cells in CHB patients undergoing NUC therapy.
• To explore the relationship between T cell responses and HBsAg levels.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was performed on sorted CD69+ CD8+ T cells from CHB patients.
• HBV-specific CD8+ T cell responses were analyzed using multicolor flow cytometry after stimulating peripheral blood mononuclear cells (PBMCs) with viral peptides.
• Analysis included assessment of polyfunctional cytokine production (IFN-γ/TNFα) and degranulation markers (CD107A/CD137).

Main Results:

• scRNA-seq identified CD8+ T cell clusters with cytolytic function transcripts in patients with high HBsAg levels.
• HBcore-specific CD8+ T cells demonstrated greater polyfunctionality compared to other HBV-specific T cells.
• A subset of HBcore-specific CD8+ T cells with reduced cytolytic activity was inversely correlated with HBsAg levels.

Conclusions:

• Qualitative differences exist in HBV-specific CD8+ T cell responses, dependent on the viral stimulant, in CHB patients on NUC therapy.
• Inducing HBcore-specific CD8+ T cells with lower cytolytic potential represents a potential novel therapeutic strategy for reducing HBsAg levels in CHB.