Using the panel of markers TNF-a, IFN-c, MIP-1b, IL-2, and CD107a, we characterized the ability of CD8 + T-cells to simultaneously exert these 'functions' in response to both HCV and HIV peptides. Figure 5 depicts a representative functional profile of virus specific CD8 + T-cells in blood and liver during HCV/HIV co-infection (Fig. 5a) and HCV mono-infection (Fig. 5b) . Analysis of co-infected subjects demonstrates a very limited functional hierarchy of HCV-specific T cells in the blood, with majority of T-cells producing one function. HIV-specific Tcells from blood had a more expanded functional hierarchy. In accordance with previous reports on HIV mono-infected individuals [16] , cells expressing all 5 functions were absent in the blood of co-infected subjects, mainly due to lack of IL-2 production. In co-infection, intra-hepatic CD8 + T-cells responding to HCV peptides were within the single-responding and 2+ populations. Intra-hepatic CD8 + T-cell responses to HIV peptides produced a larger spectrum of responses. CD107a responding cells were represented in nearly all of the different HIV-specific populations in the liver of co-infected individuals.