V delta 1T lymphocytes expressing a Th1 phenotype are the major gamma delta T cell subset infiltrating the liver of HCV-infected persons

Background: Hepatitis C infection induces an acute and chronic liver inflam mation that may lead to cirrhosis, liver failure, or hepatocarcinoma. Since the role of alpha beta T lymphocytes in hepatitis C virus (HCV) immunopath ology has been analyzed extensively, we investigated the distribution and f unctional activation of gamma delta T cell subsets in chronically HCV-infec ted patients. Materials and Methods: Blood samples and liver biopsies from 35 patients wi th compensated chronic HCV infection were compared in terms of T cell subse t distribution, expression of activation markers, gamma delta T cell recept or (TCR) repertoire, and pattern of cytokine production. Moreover, we analy zed whether these immunological parameters were associated with other clini cal observations (plasma viremia, ALT levels, Ishak index). Results: Differing from peripheral blood distribution, a specific compartme ntalization of V delta1 T cells (p < 0.001) was observed in the liver of HC V patients. These cells represented a relevant fraction of intrahepatic T l ymphocytes (1.8-8.7%) and expressed the memory/effector phenotype (CD62-L(- )CD45-RO(+)CD95(+)). This phenotype was consistent with selective homing up on antigen recognition. Mitogenic stimulation of V<delta>1(+) T lymphocytes recruited in the liver revealed the T helper cell type 1 (Th1) pattern of cytokine secretion. Interestingly, the frequency of interferon-gamma (IFN-g amma)-producing V delta1 T cells was associated with an higher degree of li ver necroinflammation. measured by the Ishak index. Finally, the T-cell rep ertoire analysis revealed the absence of V gamma selection in the TCR reper toire of intrahepatic V delta1 T cells. Conclusions: gamma delta T cell distribution in the peripheral blood differ s from the V delta1 T cell subset because it is policlonally activated and recruited in the liver of chronic HCV-infected patients. During HCV-infecti on, this T cell subset may release Th1 cytokines and contribute to the necr oinflammatory liver disease.