[CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with persistent hepatitis C virus infection].

OBJECTIVE: To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+) CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent infection of hepatitis C viruses. METHODS: Flow cytometry was used to determine the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of Foxp3 were measured by RT-PCR. RESULTS: CD(4)(+) CD(25)(+) Treg cells comprised (13.5 +/- 1.8)% of peripheral CD(4)(+) T cells in the blood of persistent hepatitis C virus infected patients, which was significantly higher than that of healthy controls (5.3 +/- 0.8)% (P = 0.004). CD(4)(+) CD(25)(+) Treg cells highly expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells dramatically suppressed the proliferation of CD(4)(+) T cells and the production of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) Treg cells in patients with persistent HCV-infection was higher than that in healthy controls (P = 0.034). These effects were dose-dependent but IL-10 and transforming growth factor beta independent. CONCLUSION: Patients with persistent hepatitis C virus infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+) Treg cells, which could function in a highly regulatory capacity to suppress Th1 response.