Μελέτη της κυτταρικής ανοσίας στην ηπατίτιδα C

Abstract

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. The immune mechanisms that promote viral persistence in HCV infection are not fully clarified. However, cellular immune responses appear to be crucial in viral control and outcome of chronic HCV infection. We studied the peripheral cellular immune responses in 34 patients with chronic HCV infection (25 with elevated and 9 with persistently normal ALT levels) and compared them with those observed in 11 individuals with past HCV infection and 24 healthy volunteers who served as controls. T cell responses to recombinant HCV proteins and synthetic peptides corresponding to known amino acid sequences of HCV core, NS3 and NS4 were analysed after specific and maximal non specific stimulation. IFN-# production was assessed using Elispot and intracellular cytokine staining and CD4+ T cell activity was measured using proliferating assays. Individuals with past HCV infection exhibited the most frequent proliferating T-cell responses against mainly non-structural HCV proteins while IFN-# production by CD8 T cells was relatively weak in comparison to patients with chronic HCV infection. Patients with chronic HCV infection and elevated ALT levels displayed an overall increased production of IFN-# after specific and non-specific stimulation. Patients with chronic HCV infection and normal ALT levels had minimal proliferating responses against whole HCV proteins but not HCV derived peptides while they exhibited an increased number of Core21-40aa-specific T cells. Conclusively, we detected enhanced proliferating activity of peripheral T cells in individuals with past HCV infection. Patients with chronic HCV infection and elevated ALT levels displayed vigorous CD8+ T cell effector responses, which appear to contribute to the establishment of HCV persistence in chronic HCV infection.