Biliary obstruction expands TREG which suppress liver T cell function (101.2)

INTRODUCTION: The mechanism by which obstructive jaundice predisposes to infection has not been clearly defined. We hypothesized that extrahepatic biliary obstruction would directly impair the function of T cells within the liver. METHODS: Bile duct ligation (BDL) or sham laparotomy (SL) was performed in mice. Liver or spleen T cell function was assessed by proliferation in response to dendritic cells or anti-CD3 stimulation. TREG (CD4+CD25+FoxP3+) were measured by flow cytometry. CD4+C25+ (70% FoxP3+) liver T cells were purified by FACS and used as suppressors. RESULTS: Following BDL, liver T cells were markedly less responsive to allogeneic or antigen-loaded syngeneic dendritic cells. In contrast, spleen T cell function was preserved. Even in the presence of direct anti-CD3 stimulation, liver T cells from BDL mice were functionally deficient and produced less IL-2 relative to spleen T cells. BDL expanded the number of liver TREG which suppressed the response of CD4+C25− T cells to DC in vitro. CONCLUSION: BDL expands TREG, which may contribute to the increased risk of infection in patients with obstructive jaundice.