Subsets in the Peripheral Blood and Liver

The differentiation and functional status of virus-specific CD8 T cells is significantly influenced by specific and ongoing antigen recognition. Importantly, the expression profiles of the interleukin-7 receptor alpha chain (CD127) and the killer cell lectin-like receptor G1 (KLRG1) have been shown to be differentially influenced by repetitive T-cell receptor interactions. Indeed, antigen-specific CD8 T cells targeting persistent viruses (e.g., human immunodeficiency virus and Epstein-Barr virus) have been shown to have low CD127 and high KLRG1 expressions, while CD8 T cells targeting resolved viral antigens (e.g., FLU) typically display high CD127 and low KLRG1 expressions. Here, we analyzed the surface phenotype and function of hepatitis C virus (HCV)-specific CD8 T cells. Surprisingly, despite viral persistence, we found that a large fraction of peripheral HCV-specific CD8 T cells were CD127 and KLRG1 and had good proliferative capacities, thus resembling memory cells that usually develop following acute resolving infection. Intrahepatic virus-specific CD8 T cells displayed significantly reduced levels of CD127 expression but similar levels of KLRG1 expression compared to the peripheral blood. These results extend previous studies that demonstrated central memory (CCR7) and early-differentiated phenotypes of HCV-specific CD8 T cells and suggest that insufficient stimulation of virus-specific CD8 T cells by viral antigen may be responsible for this alteration in HCV-specific CD8 T-cell differentiation during chronic HCV infection