Recent lines of evidence demonstrate the importance of the qualitative rather than quantitative characteristics of CD8 + T-cell responses to efficient viral control [13, 27] . The significance of Tcell populations simultaneously representing 5 different functions has been discussed as a hierarchical functional model in viral infections such as CMV and EBV which are effectively controlled by respective CD8 + T-cells [16] . HCV-specific CD8 + T-cells were not poly-functional which is consistent with the notion that although HCV-specific T-cells are found in hepatic tissue, their loss of poly-functionality may be associated with inefficient control of HCV replication. HIV-specific T-cells in the liver of co-infected individuals however, simultaneously could express 4 and 5 of the measured markers. Recently, T-cell exhaustion has been related to signaling pathways through PD-1 [28, 29] . Our analysis of PD-1 levels of antigen-specific CD8 + T-cells from co-infected liver demonstrates higher expression of PD-1 on HCV-specific T-cells, compared to those specific for HIV, supporting the notion that the former are less functional. The observed poly-functionality of intra-hepatic HIV-specific T-cells, should have little effect on HCV replication but would further enhance the cytokine milieu induced from bystander activation, and contribute to liver damage during co-infection with HCV. In this regard, we found that the degranulation marker CD107a dominates the HIV-specific CD8 + T-cell responses in the liver, with the majority of the responding cells expressing CD107a, a surrogate marker for the cytotoxic function of CD8 + T-cells. Activated HIV-specific CD8 + T-cells with the potential to degranulate could induce bystander damage. In addition, the release of chemokines such as MIP-1b by the same cells could also attract further lymphocytes without HCV specificity to the liver. Bystander function of these non-specific T-cells could expand the tissue damage triggered by HCV infection and ultimately activate fibrogenesis.