Background:  Phenotypic and functional characterization of several virus-specific T cell responses including cytomegalovirus (CMV), Epstein-Barr virus (EBV), and HIV-1 have been performed in the last years. However, these parameters have only sporadically been assessed for hepatitis C virus (HCV)-specific T cell responses. The influence of HIV-1 co-infection on the function of HCV-specific T cells has also rarely been addressed. We therefore aimed to investigate and compare these issues in the context of HCV mono-infection and HIV/HCV co-infection.

Methods:  HCV-specific CD4⁺ and CD8⁺ T cells from chronically HCV mono-infected (n = 10) and HIV/HCV co-infected (n = 8) individuals were tested for proliferation using the CFSE dye assay after stimulation with the cognate peptide. In addition, profiles of interferon-g (IFN-g) and interleukin-2 (IL-2) secretion and of differentiation markers (CD45RA and CCR7) expression by specific T cells were analyzed by multi-color flow cytometry.

Results:  Both CD4⁺ and CD8⁺ HCV-specific T cells from HCV mono-infected individuals were clearly able to proliferate after 5 to 7 days stimulation with the corresponding HCV-derived peptide in absence of exogenous help such as IL-2. Most interestingly, HCV-specific T cells from HIV/HCV-co-infected individuals exerted a similar proliferation potential. In addition, in contrast to what has been observed for HIV-1-specific CD4⁺ and CD8⁺ T cells which are composed exclusively of IFN-g-secreting cells in the untreated chronic phase of infection, HCV-specific T cells displayed a poly-functional profile of cytokine secretion, with CD4⁺ T being composed of single IL-2, double IFN-g/IL-2 and single IFN-g-secreting cells and CD8⁺ T cells of double IFN-g/IL-2 and single IFN-g-secreting cells. This profile was observed for both HCV mono-infected and HIV/HCV co-infected patients. Finally, HCV-specific CD4⁺ and CD8⁺ T cells were found predominantly in the CD45RA^­ CCR7^­ effector memory subset but were also observed in the CD45RA^­ CCR7⁺ central memory subset.

Conclusions: The presence of polyfunctional HCV-specific T cells indicates a preservation of immune functions in HCV infection and it may be consistent with a slower progression of HCV compared to HIV infection.