[In vitro expansion of antigen-specific natural regulatory T cells in hepatitis C virus infection mediated by Core antigen]

ABSTRACT

Hepatitis C virus [HCV] is one of the most relevant persistent infections afflicting the human population. Control of viral replication in HCV infection has been associated with the cellular component of the host immune response. Several mechanisms have been proposed to explain this abnormal immune response, among them an altered activity of regulatory T cells [Tregs] being the most recently postulated. As the first report, in the present study the ability of HCV-core antigen in increase the frequency of natural Tregs [nTregs] in the mixed population of PBMCs was evaluated. Peripheral blood mononuclear cells [PBMCs] from chronic HCV infected patients [n=19] and normal controls [n=6] were analyzed to study the effect of HCV-core antigen in frequency of HCV specific nTregs. For this, PBMCs of different groups were isolated, cultured and stimulated with core antigen. Then an in-house triple-stain flowcytometric method was used to investigate the frequency of nTregs. The results showed that, following incubation with HCV-core Ag, a population of nTregs was increased but, in negative controls the number of nTregs did not increase. The present data supporting the idea that nTregs are able to respond specifically to HCV antigen suggests that Tregs could contribute to an inadequate response against the HCV infection, leading to chronic infection and supports the view that specific natural Tregs may be implicated in host immune tolerance during HCV infection. It is reasonable that HCV vaccine candidates avoid epitopes that lead to strong nTregs stimulation