To our knowledge, this is the first study to determine CD8+ Tregs in HCV-infected patients and in HIV/HCV co-infected patients. The elevated frequencies of CD4+ Tregs and CD8+ Tregs in HCV-infected and HIV/HCV co-infected patients might illustrate the necessity for the immune system to limit a vigorous immune response against the chronic viral infection, while favouring persistent viral infection. Whether the increased

frequencies of CD4+ Tregs and CD8+ Tregs as well as chronic immune activation (CD38+ HLA-DR+) in co-infected patients compared with HCV-infected patients have any relation to the increased risk of fibrosis progression MK-8669 in patients with HIV co-infection is uncertain, keeping in mind that we found no differences in CD4+ Tregs, CD8+ Tregs or T cell activation between HCV-infected patients with or without fibrosis. Microbial translocation is known to be a key contributor to

the elevated chronic immune activation found in HIV-infected Selleck SAHA HDAC patients [22]. Furthermore, microbial translocation has been found to be associated with progression of fibrosis in HCV patients [23]. Further studies assessing the impact of microbial translocation on the increased risk of fibrosis progression in HIV/HCV co-infection are warranted. The function of Tregs in HCV-infected and HIV/HCV co-infected patients has not been described. Recently, it was demonstrated that co-expression of CD45RA and Foxp3 can be used to further characterize CD4+ Tregs into three functionally distinct subpopulation, that is, resting Tregs (CD45RA+ Foxp3low), activated Tregs (CD45RA− Foxp3high) and non-suppressive Tregs (CD45RA− Foxp3low) [31]. Resting and activated Tregs represent two stages of differentiation and both have active Foxp3 gene transcription and suppressive activity. In contrast, the non-suppressive Tregs are characterized by an unstable Foxp3 expression, high production of IL-2 and IFN-γ, and no suppressive Protirelin activity. Thus, the non-suppressive Tregs may illustrate activated cells transiently expressing Foxp3. In our cohort, lower frequencies of resting Tregs as well as higher frequencies

of activated Tregs were found in HCV-infected and HIV/HCV co-infected patients compared with healthy controls. Probably due to the limited study population, significant differences of activated Tregs were only observed between HCV infected without fibrosis and healthy controls. Thus, CD4+ Tregs in patients with chronic HCV infection and especially in patients with HIV/HCV co-infection seem to be functionally more activated. However, the frequency of non-suppressive Tregs was also higher in HCV infected with fibrosis indicating that a considerable fraction of CD4+ Tregs in this patient group may in fact be activated cells with no suppressive capacity. Furthermore, to evaluate whether elevated frequency of Tregs resulted in altered cytokine production, production of the cytokine IL-10 was measured in PBMC.