CD8+ T cell responses specific for hepatitis B virus core protein in patients with chronic hepatitis B virus infection.

ABSTRACT

BACKGROUND: Chronic hepatitis B virus (HBV) infection includes a set of heterogeneous clinical patterns, and core-protein-specific T cell response is important for virus control and disease progression, yet is not well elucidated. OBJECTIVES: To analyze the phenotypic and functional profiles of HBV-core-protein-specific CD8+ T cells in different clinical patterns of chronic HBV infection. STUDY DESIGN: A total of 46 HBV patients were recruited and classified according to their clinical status. CD8+ T cell responses in different patterns of chronic HBV infections were tested with flow cytometry using overlapping 15-mer peptides covering HBV core protein. Meanwhile, the CCR7/CD27 phenotypes of these CD8+ T cells were also determined. RESULTS: Frequencies of gamma interferon (IFN-γ) positive CD8+ T cells in inactive HBV surface antigen (HBsAg) carriers in response to the core protein peptide pools were generally stronger than those of chronic HBV carriers and resolved individuals, especially with regards to peptide pool C13-C24. Moreover, phenotypic studies further highlighted the group of CD8+ CCR7-CD27+ T memory cells, which showed significantly higher levels of IFN-γ secretion in inactive HBsAg carriers than those in chronic hepatitis B patients, chronic HBV carriers and resolved individuals. CONCLUSIONS: Core-protein-specific T cell response plays an important role in chronic HBV infection. Inactive HBsAg carriers showed a much stronger core-protein-specific cytotoxic T cell response than other types of chronically infected patients. CD8+ CCR7-CD27+ T memory lymphocytes may be crucial in the immune pathogenesis of chronic HBV infection.