Th1 down-regulation at the single-lymphocyte level in HCV-related liver cirrhosis and the effect of TGF-β on Th1 response: possible implications for the development of hepatoma

Abstract

Patients with hepatitis C virus (HCV) related-liver cirrhosis (LC) often develop hepatoma. The type 1 helper T cell (Th1) response presents an antitumor effect. We evaluated the Th1 response in patients with HCV-related LC at the single-cell level and examined the influence of transforming growth factor (TGF)-β, an immunosuppressive cytokine, on the Th1 response. We determined the ratios of Th1-type cytokine (IFN-γ, IL-2)-producing cells to CD3-positive cells in 14 patients (LC group) and in 16 normal controls using flow cytometry and measured serum TGF-β 1 and TGF-β 2 levels by ELISA. We then incubated, peripheral blood mononuclear cells from seven healthy volunteers with recombinant TGF-β 1 or TGF-β 2 for 48 h, and determined the ratio of IFN-γ producing cells to CD3-positive cells. The IFN-γ ratio was significantly lower in the LC group (29.7±0.3 vs. 44.2±15.0%, P<0.01). The serum TGF-β 2 level was significantly increased in the LC group (601±232 vs. 329±118 pg/ml, P<0.001). TGF-β 2 significantly suppressed IFN-γ production at the single-cell level (10.0±4.3 vs. 7.3±2.0%, P<0.05). These findings indicated that the enhanced down-regulation of Th1 by TGF-β 2 in patients with HCV-related LC might be effective against hepatoma.