Background: Co-infection with HIV increases HCV chronicity, accelerates liver disease, and increases mortality. Little is known about the role of HCV-specific cellular immune responses in HIV/HCV co-infected individuals. While pro-inflammatory cytokines such as interleukin-2 (IL-2) and interferon-g (IFN-g) promote cell-mediated immunity and viral clearance, they may also contribute to immunopathology. Conversely, while immunosupressive cytokines such as interleukin 10 (IL-10) down-regulate cell-mediated immunity and immunopathology, they may promote chronic infection and immunodeficiency.  The goal of this study was to investigate HCV-specific cellular immune responses in peripheral blood mononuclear cells (PBMC) from HIV/HCV co-infected individuals. 

Methods: 30 individuals participated in this study. Intact or T-cell depleted PBMC from 12 HIV/HCV co-infected, 10 HIV-infected, and 8 uninfected control individuals were incubated overnight with recombinant HCV proteins (core, NS3, and NS4) and the percentage of cells producing IL-10, IL-2, and IFN-g was estimated by intracellular flow cytometry. Antibodies to various lymphoid and myeloid cell surface markers distinguished subpopulations of cells. PBMC from 11 co-infected patients were incubated for 5 days with HCV core, NS3, or NS4, Candida recall antigen or PHA and pulsed for 16 hours with ³H-thymidine to measure T-cell proliferation. A stimulation index (cpm test antigen/ cpm background)  > 3 was considered positive. Statistical analysis of flow cytometry results utilised the Student paired t-test where n>10 and the Mann-Whitney U test where n<10.

Results: Spontaneous IL-10 production occurred during overnight incubation of both intact and T cell depleted PBMC. After T-cell depletion, the percentage and absolute number of cells producing IL-10 in response to HCV proteins increased. The IL-10 producing cells were not B cells or NK cells, but did express CD36. The percentage of CD36+, IL-10 producing cells in both HIV/HCV co-infected and HIV infected individuals increased significantly (p<0.05) following incubation with HCV proteins. No HCV-specific IL-2 or IFN-g production was detected. HCV-specific T-cell proliferation against NS3 (stimulation index=4.2) was detected only in PBMC from individuals without HCV protein induced IL-10 production.

Conclusions: CD36+ mononuclear cells from HIV-infected and HCV co-infected individuals spontaneously produce IL-10. Production of IL-10 increases following exposure to HCV proteins or T-cell depletion and is associated with the absence of HCV-specific T-cell proliferation. This suggests that induction of IL-10 by HCV proteins may down-regulate cell-mediated immune responses against HCV and other pathogens in HIV-co-infected individuals, especially when HIV associated T-cell depletion has occurred.