Increased frequency of late-senescent T cells lacking CD127 in chronic hepatitis C disease.

CHRONIC hepatitis C; T cells; INTERLEUKINS; VIRAL replication; IMMUNE response; BIOMARKERS

Background Hepatitis C virus ( HCV) causes persistent disease in ~85% of infected individuals, where the viral replication appears to be tightly controlled by HCV-specific CD8+ T cells. Accumulation of senescent T cells during infection results in considerable loss of functional HCV-specific immune responses. Materials and methods We characterized the distinct T-cell phenotypes based on the expression of costimulatory molecules CD28 and CD27, senescence markers PD-1 and CD57, chronic immune activation markers CD38 and HLA- DR, and survival marker CD127 ( IL-7 R) by flow cytometry following activation of T cells using HCV peptides and phytohemagglutinin. Results HCV-specific CD4+ and CD8+ T cells from chronic HCV ( CHC) patients showed increased expression of PD-1. Furthermore, virus-specific CD4+ T cells of CHC-infected subjects displayed relatively increased expression of HLA- DR and CD38 relative to HCV-specific CD8+ T cells. The CD4+ and CD8+ T cells from HCV-infected individuals showed significant increase of late-differentiated T cells suggestive of immunosenescence. In addition, we found that the plasma viral loads positively correlated with the levels of CD57 and PD-1 expressed on T cells. Conclusions Chronic HCV infection results in increased turnover of late-senescent T cells that lack survival potentials, possibly contributing to viral persistence. Our findings challenge the prominence of senescent T-cell phenotypes in clinical hepatitis C infection. [ABSTRACT FROM AUTHOR]