007). Finally, non-suppressive Tregs were significantly higher in HCV infected with

fibrosis compared with healthy controls (P = 0.012) (Fig. 4C). The frequencies of CD8+ Tregs showed the same pattern as CD4+ Tregs. There was a significantly higher frequency of CD8+ Tregs in the co-infected patients (1.0%; 0.7–1.2) compared with BMS-777607 HCV-infected patients without fibrosis (0.5%; 0.3–0.7, P < 0.001) and healthy controls (0.4%; 0.4–0.5, P < 0.001) (Fig. 3B). However, among HCV mono-infected patients, the frequency of CD8+ Tregs was only elevated in patients with fibrosis (0.6%; 0.4–0.8) compared with healthy controls (P < 0.05). Finally, the frequencies of Th17 cells were found to be very similar in all four groups (data not shown). The intrahepatic presences of Tregs were determined in the portal triad in 12 HCV-infected patients to evaluate a potential association with the level of intrahepatic Tregs and

the degree of intrahepatic inflammation and fibrosis (Fig. 5A). The amount of Tregs in portal triads was associated with the degree of intrahepatic inflammation activity assessed by METAVIR activity score (ρ = 0.620, P < 0.05) AZD1208 molecular weight (Fig. 5B), but no correlation was found between the amount of intrahepatic Tregs and liver fibrosis (P = 0.5). Furthermore, the amount of Tregs in portal triads was significantly associated with the level of CD8+ Tregs in peripheral blood (ρ = 0.627, P < 0.05) (Fig. 5C). A similar association was not found for either CD4+ Tregs (P = 0.4) or the total frequency of Tregs in peripheral blood Liothyronine Sodium (P = 0.6). Hepatitis C virus-infected patients with and without fibrosis presented with higher levels and higher productions per lymphocyte of IL-10 compared with co-infected patients and healthy

controls (P < 0.05, Table 2). Furthermore, co-infected patients presented with low levels and production of IL-10 compared with healthy controls (P < 0.05). We found no correlation between the level of IL-10, IL-17 or TGF-β and the level of fibrosis, activated T cells or Tregs in the study groups. This study was designed to find associations between pro- and anti-inflammatory T cell subsets in peripheral blood and the stage of liver fibrosis in patients with chronic HCV infection and in patients co-infected with HIV. Furthermore, intrahepatic Tregs in liver tissue were determined to find associations to liver inflammation activity, liver fibrosis and to Tregs in peripheral blood. Frequencies of anti-inflammatory CD4+ and CD8+ Tregs in peripheral blood were higher in patients with HCV infection compared with healthy controls, and even higher in patients with HIV/HCV co-infection. Furthermore, CD4+ Tregs in HCV-infected individuals displayed an activated phenotype and in HCV-infected with fibrosis also a non-suppressive phenotype. Frequencies of pro-inflammatory Th17 cells were unrelated to infection with HCV.