Cellular Immune Responses Against Hcv: T Cells Take A Diversion in the Liver

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.