Hepatic expansion of a virus-specific regulatory CD8+T cell population in chronic hepatitis C virus infection.

Regulatory T (TR) 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-g production) in patients with chronic hepatitis C virus (HCV) infection because
of the concomitant presence of virus-specific CCR7–CD8+ TR cells producing considerable amounts of IL-10.
These CD8+ TR 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 for the first time to
our knowledge direct evidence of the existence of virus-specific CD8+ TR 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.