However, in patients co-infected with HIV, lower production of IL-10 was found. This is in agreement with the previous finding [53, 54] and may be the result of IL-10 in HIV-infected patients primarily being produced in monocytes as opposed to healthy individuals Selleckchem CH5424802 where IL-10 mainly is produced in lymphocytes, although both cell populations contribute to the production of IL-10 in both healthy and HIV-infected individuals. However, the golden

standard for evaluating functional characteristics in Tregs is suppression assays. Future studies using these methods are needed to completely understand the functional characteristics of CD4+ Tregs in patients with chronic HCV infection and HIV/HCV co-infection. In liver tissue, a positive correlation between intrahepatic Tregs and intrahepatic inflammation

was found, suggesting that Tregs are related to ongoing inflammation, and may be a response of the immune system to limit destructive inflammatory activity in the liver parenchyma. Interestingly, Tregs were not associated with fibrosis or cirrhosis, where the degree of active inflammation may have settled down. Likewise, previous studies have demonstrated increased intrahepatic CD4+ Tregs in HCV-infected patients, and no association between CD4+ Tregs and liver fibrosis [15, 55]. However, one study [12] found a significant inverse correlation between the level of intrahepatic CD4+ Tregs and METAVIR fibrosis score. The role selleck products of CD8+ Tregs in HCV-infected patients is yet unclear. Interestingly, HCV-specific CD8+ T cells with suppressive capacity via IL-10 have been isolated from the liver [56, 57]. Furthermore, in one study, HCV-specific intrahepatic CD8+ IL-10-producing cells located to areas with limited fibrosis have been demonstrated [58]. A positive correlation

between intrahepatic Tregs and CD8+ Tregs in peripheral blood was found. As only 12 patients with liver biopsies contributed to this analysis, interpretation is rather speculative, but the positive correlation may suggest that the level of CD8+ Tregs in peripheral blood reflects the level in liver tissue. Alternatively, intrahepatic Tregs are CD4+ Tregs homing to inflamed liver tissue, and consequently Tregs in peripheral blood do not reflect the much level of Tregs in liver tissue. Thus, whether findings in peripheral blood reflect the amount of intrahepatic lymphocytes is still uncertain as other studies also present with contradictory results [12, 15, 55]. Further studies combining the expression of Foxp3 with the expression of CD4 and CD8 are warranted to investigate the role and phenotype of Tregs in liver tissue in HCV pathogenesis. No difference in the frequency of Th17 cells or levels of IL-17 between our study groups was found. Thus, it seems unlikely that the frequency of Th17 cells in peripheral blood is associated with progression of liver fibrosis in patients with chronic HCV infection.