Background:  Hepatitis C virus (HCV) -related liver disease contributes to the morbidity and mortality of persons with HIV infection. Some studies have shown an increase in the rate of progression of HCV-related liver disease in persons with HIV co-infection compared with persons with HCV mono-infection, but the mechanism of this enhanced liver injury in co-infected persons is poorly understood. HIV infection itself is associated with increased immune activation of peripheral blood T cells (bystander activation), so we hypothesized that liver-infiltrating CD8⁺ T cells from patients with HIV/HCV co-infection would show increased activation in comparison with cells from persons with HCV mono-infection. 

Methods:  We studied 11 patients with HIV/HCV co-infection (with HIV control on HAART) and 20 patients with HCV mono-infection undergoing liver biopsy. We analyzed the frequency of liver infiltrating CD8⁺ T cells expressing the activation markers CD69, CD38, and HLA-DR, and the senescence marker, CD57 using fluorescence-activated cell sorting (FACS) analysis. Unpaired t-tests were used to compare the mean expression of each marker between the 2 groups. Additionally, tetramers were used to evaluate the expression of activation markers on liver-infiltrating HIV- and HCV-specific CD8⁺ T cells from 2 patients with HIV/HCV co-infection and 2 patients with HCV mono-infection. 

Results:  A greater frequency of liver infiltrating CD8⁺ T cells from patients with HIV/HCV co-infection expressed CD38 (59% vs 45%, p = 0.05), HLA-DR (68% vs 49%, p = 0.02), and CD57 (29% vs 19%, p = 0.02) in comparison with HCV mono-infection. No difference in CD69 expression (p = 0.2) could be detected. A majority of liver infiltrating HIV- and HCV-specific CD8⁺ T cells from HIV/HCV-co-infected and HCV-mono-infected patients expressed markers of activation, however, small numbers of patients with detectable liver tetramer responses precluded statistical comparison. 

Conclusions:  Liver-infiltrating CD8⁺ T cells show greater activation in patients with HIV/HCV co-infection than in patients with HCV mono-infection. Greater expression of CD57 in the co-infected patients could represent a later stage of differentiation for these cells. This could contribute to the increased rate of liver disease progression in HIV/HCV co-infection if the cells expressing these activation and differentiation markers have greater cytotoxic effector potential and/or produce greater amounts of pro-inflammatory/pro-fibrotic cytokines.