Antigen-specific IL-10 Producing CD4+,CD25+ Regulatory T Cells in Chronically Infected HCV Patients

The mechanism behind the apparent lack of effective antiviral immune esponse in patients with chronic hepatitis C irus (HCV) infection is poorly understood. Although multiple levels of abnormalities have been dentified in innate and daptive immunity, it is postulated that production of specific cytokines such as IL-10 aycontribute to the induction and maintenance of HCV persistence. Production of IL-10 by CD4+,CD25+,IL-10+ regulatory T cells with regulatory capacity (Tregs) appears to be one of the viral mechanisms that alter the antiviral immune response. As the first report, that attempts to mimic physiological forces that can occur during HCV infection, in this study we evaluate the ability of HCV-core antigens in increasing the frequency of CD4+,CD25+,IL-10+ regulatory T cells. We analyzed peripheral blood mononuclear cells (PBMCs) from chronic HCV-infected patients (n and normal controls (n=6) to determine the effect of the HCV-core antigen in the frequency of HCV-specific IL 10 production. PBMCs of different groups were isolated, cultured and stimulated with core antigen. Then, an in house triple-stain flow cytometric method was used to investigate the frequency of CD4+,CD25+,IL-10 producing cells. Following incubation of PBMCs with HCV-core antigen, a population of CD4+,CD25+,IL-10+ cells (regulatory T cells) increased. However we observed no increase in Tregs in the negative controls. The study supports the view that specific CD4+,CD25+,IL-10+ T cells may be implicated in host immune tolerance during an HCV infection. It is likely that HCV vaccine candidates avoid epitopes that lead to strong IL-10 production.