Editing Hbv Into Oblivion

Abstract

Regulatory T (T(R)) cells consist of phenotypically and functionally distinct CD4 ؉ and CD8 ؉ T-cell subsets engaged both in maintaining self-tolerance and in preventing anti-non-self effector responses (microbial, tumor, transplant, and so on) that may be harmful to the host. Here we propose that the proinflammatory function of virus-specific memory effector CCR7 ؊ CD8 ؉ T cells, which are massively recruited in the liver, are inefficient (in terms of IFN-gamma production) in patients with chronic hepatitis C virus (HCV) infection because of the concomitant presence of virus-specific CCR7 ؊ CD8 ؉ T(R) cells producing considerable amounts of IL-10. These CD8 ؉ T(R) cells are antigen specific, as they can be stimulated by HCV epitopes and suppress T-cell responses that are in turn restored by the addition of neutralizing anti-IL-10. This study provides direct evidence of the existence of virus-specific CD8 ؉ T(R) cells that infiltrate the livers of patients with chronic HCV infection, identifies IL-10 as a soluble inhibitory factor mediating suppression, and suggests that these cells play a pivotal role in controlling hepatic effector CD8 ؉ T-cell responses.