Oligoclonal CD8+ T-Cell Expansion in Patients with Chronic Hepatitis C Is Associated with Liver Pathology and Poor Response to Interferon-α Therapy

The role of CD8+ T lymphocytes in chronic hepatitis C virus (HCV) infection and in liver injury with subsequent development of fibrosis and cirrhosis is poorly understood. To address this #x003Fion, we performed a follow-up study including 27 chronically HCV-infected individuals. We determined clonality and phenotypes of circulating CD8+ T cells employing TCRBV spectratyping. Antigen specificity was tested by rMHC-peptide tetramer staining and stimulation with recombinant HCV antigens. In addition, T-cell clonality and phenotypes were followed during the variable clinical response of interferon- (IFN) α treatment. We could demonstrate that CD8+ T-cell expansions were significantly associated with liver fibrosis and cirrhosis. Likewise, increased oligoclonality of circulating CD8+ T cells in chronic HCV infection was identified as an indicator for poor clinical response to IFN-α therapy. Moreover, we also found that IFN-α therapy enhanced the differentiation of CD8+ T cells towards a late differentiation phenotype (CD28− CD57+). In cases of virus elimination the disappearance of expanded terminally differentiated CD8+ cells was observed. Thus, this study identifies an association of clonal expansions of circulating CD8+ T cells with liver pathology and provides a possible explanation for the fact that response to IFN-α therapy diminishes with the duration of infection.