Background: In patients chronically infected with hepatitis C virus (HCV), whether co-infected or not with HIV, T-cell responses are often undetectable in peripheral blood. We analyzed the strength and specificity of HCV-specific CD8 and CD4 T-cell responses in the liver of HCV/HIV co-infected and HCV mono-infected patients.

Methods:  Liver biopsies from 10 HCV/HIV patients (median CD4 count: 456/mm³; ranges: 283 - 630) and 8 HCV patients were studied. CD8 and CD4 T cells were expanded from the intrahepatic lymphocytes. CD8 T cells were co-cultured with autologous EBV-transformed B-cell lines infected with recombinant vaccinia viruses expressing the HCV core/E1, E2(NS1)/NS2, E2/NS2/NS3, NS4, NS5a, and NS5b or a control gene (lac). A pool of cytomegalovirus, Epstein Barr and influenza virus peptides (CEF) was used as a control. CD4 T cells were co-cultured with recombinant HCV proteins (core, NS3, and NS5) and irradiated autologous PBMC. Virus-specific interferon-g production was determined by ELISA. Results were expressed in number of spot-forming-cells (SFC)/1x10⁶ cells and analyzed individually for each studied HCV protein as well as a sum of responses using nonparametric statistics.

Results:  A vigorous and polyclonal intrahepatic CD8 response to HCV were detected in 7/10 HCV/HIV patients with median total frequencies of 638 SFC/1x10⁶ cells (range: 14 - 5700) and were not significantly different from those in HCV patients, detected in 7/8 patients (median; range: 647; 10 - 1941). Responses to CEF were significantly higher in coinfected (1927; 47 - 4000) than in mono-infected (393; 0 - 1433)(p = 0.04). Intrahepatic lymphocytes versus PBMC anti-HCV CD8 responses were compared for 3 patients and found to be higher in the liver than in peripheral blood. Intrahepatic CD4 responses also did not differ between HCV/HIV and HCV patients (32 and 81 SFC/1x10⁶ cells, respectively; 0 - 235). Interestingly, there was a positive correlation between intrahepatic CD8 and CD4 responses to HCV (r = 0.59, p = 0.03). Intrahepatic CD8 responses were not correlated with CD4 counts or liver disease in this small cohort.

Conclusion:  These results show a presence of vigorous and polyclonal HCV-specific CD8 T-cell responses in the liver of patients with chronic hepatitis C even in the presence of HIV, which correlated with intrahepatic HCV-specific CD4 responses, but not with peripheral CD4 counts. Future studies will determine the role of these cells in liver fibrosis.

Keywords: Hepatitis C; T cell immune response; liver