Influence of HIV co-infection on hepatitis C immunopathogenesis

Abstract

The role of CD4(+) or CD8(+) T cells in chronic hepatitis C virus (HCV) infection is unclear. People with chronic infection have weak responses against HCV in the blood, but HCV-specific responses are present within liver. The prevailing hypothesis of liver injury in HCV is that CD4(+) and CD8(+) T cell responses mediate HCV-related liver damage but are ineffectual at clearing the chronic infection. However, we recently reported that vigorous CD4(+) responses that produce interferon gamma (IFNgamma) early in infection are correlated with slower rates of disease progression, and compartmentalize to the liver. People with chronic HIV and HCV co-infection, particularly those with CD4(+) <200 cells/mm(3), have a higher rate of fibrosis development and severe liver disease. Co-infected people have variable degrees of immunosuppression that may provide insight into the relationship between cellular immune functions and the degree of liver damage as assessed by liver biopsy. People with co-infection may have quantitative or qualitative differences in the immune responses. We recently found a relationship between CD4(+) immune responses and liver histology. There are qualitative differences in the CD4(+) responses found in the liver in co-infected people compared to those with HCV alone, whereas no such differences are found when CD8(+) responses are measured. Neither CD4(+) nor CD8(+) responses correlate with the peripheral CD4 count.