Analysis of CD127 and KLRG1 expression on hepatitis C virus-specific CD8+ T cells reveals the existence of different memory T-cell 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.