The phenotype of hepatitis B virus–specific T cells differ in the liver and blood in chronic hepatitis B virus infection

Hepatitis B virus (HBV)‐specific T cells play a key role in clearance of the virus and in the pathogenesis of liver disease. Peripheral blood (n = 25) and liver biopsies (n = 19) were collected from individuals with chronic untreated HBV infection. Whole blood, cultured peripheral blood mononuclear cells (PBMCs), and cultured liver‐infiltrating lymphocytes (LILs) were each stimulated with an overlapping peptide library to the whole HBV genome. The expression of T helper 1 (Th1) cytokines [interferon gamma (IFN‐γ), tumor necrosis factor alpha (TNF‐α), and interleukin 2 (IL‐2)] and interleukin 10 (IL‐10) was analyzed by intracellular cytokine staining and flow cytometry. In ex vivo whole blood, more lymphocytes produced Th1 cytokines than IL‐10. When comparing cultured LILs with cultured PBMCs, we found a significantly higher magnitude of CD8+ T cells from the liver producing IL‐10 (P = 0.044), primarily in hepatitis B e antigen positive (HBeAg+) individuals. A positive correlation resulted between the magnitude of HBV‐specific TNF‐α+ CD4+ T cells in the liver and the degree of liver inflammation and fibrosis (P = 0.002 and P = 0.006, respectively). Conclusion: The differences in cytokine production from HBV‐specific T cells in blood and liver may explain the capacity for HBV to persist in the absence of significant hepatic destruction and highlights the balance between cytokine‐mediated viral control and liver damage. (HEPATOLOGY 2007.)