This is the first study to demonstrate the presence of HIVspecific T-cells within the liver of HCV/HIV co-infected individuals. The finding of HIV-specific T-cells within liver of co-infected individuals may not altogether be surprising, given the high frequencies of HIV-specific CD8 + T-cells found in the peripheral blood in untreated HIV infection. Nevertheless, it is surprising to find functional T-cells of such viral specificities to be accumulating in liver. In contrast, we could not detect CMVspecific T-cells in co-infected liver despite their abundance in blood indicating that different viruses target T-cells to the liver. Recent studies have demonstrated that systemic viral infections may recruit viral-specific T-cells to the liver. The significance of non-hepatotropic viral-specific T-cells that are found in liver is unclear. It has been postulated that the liver can non-selectively trap activated T-cells during any infection, and thus act as a 'sink' or 'graveyard' [18] , however it is unclear whether these cells are rendered anergic while traveling in the liver or contribute to inflammation and damage as a result of bystander activation. Of note, is that hepatitis has been observed in measles [19] , SARS [20] and in 20% of individuals with acute HIV infection [21] . Polakos et. al. [22] found that some individuals infected with influenza-A develop transaminitis and showed in a murine influenza model that influenza-specific CD8 + T-cells migrate to Figure 3 . Polychromatic FACS analysis of viral-specific T cells in HCV/HIV co-infection. Shown are representative FACS data of the HIV and HCV specific multi-parameter CD8 + T-cell responses from (a) liver and (b) blood of subject OM 405, a therapy-naïve HCV/HIV co-infected individual, after in vitro stimulation using pool of HIV and HCV peptides. Initial gating on forward scatter area (FSC-A) versus height (FSC-H) was used to remove doublets. The events were further gated on forward scatter (FSC) versus the dead cell marker to remove dead cells. Lymphocytes were gated on the remaining live cells on a FSC versus SSC plot. Gates on CD3 + /CD8 + cells were then generated. All responses are gated on a CD3 + /CD8 + population and presented against TNF-a on the x-axis. Figure (c) shows a comparison of the frequency of HIV and HCV-specific CD8 + T-cells in the liver and blood of therapy-naïve, co-infected individuals. All intra-hepatic HCV-specific responses are significantly stronger than peripheral HCV-specific responses. doi:10.1371/journal.pone.0003454.g003 Non-hepatotropic viruses such as HIV, CMV and EBV, in general do not induce chronic hepatitis, thus, it is possible that the coexistence of hepatotropic viruses may alter the hepatic environment to allow recruitment of activated T-cells non-specifically. This could be due to an up-regulation of integrins such as ICAM-1 and VCAM-1 in hepatic sinusoids as previously shown during HCV infection [23] that could enhance T-cell recruitment. In this regard, Spangenberg et. al. [24] demonstrated the presence of influenza-specific T-cells in about 50% of liver biopsies from HCV mono-infected individuals.