T_CD8 response in diverse outcomes of recurrent exposure to hepatitis C virus

To analyse the immune correlates in a setting of recurrent exposure to hepatitis C virus (HCV), we studied T_CD8 responses in injecting drug users (IDUs) with different disease outcomes. Ex vivo HCV-specific T _CD8 responses assessed by interferon-γ (IFNγ) enzyme-linked immunospot (ELISPOT) were comparable in human lymphocyte antigen (HLA)-matched IDUs with spontaneous HCV clearance or persistent infection. A detailed characterization of these T_CD8 cells in age and HLA-matched IDUs demonstrated that HCV clearance and protection from reinfection correlated with HCV-specific T_CD8 cells that could proliferate in vitro, possessed cytotoxic potential and produced IFNγ and tumour-necrosis factor-α, rather than with the circulating frequency of responding T _CD8 cells determined ex vivo. While validating the importance of multifunctional T_CD8 in mediating protection in IDUs with recurrent exposure to HCV our findings highlight that the magnitude and/or breadth of HCV-specific T_CD8 determined in ex vivo ELISPOT may not be the sole determinant of protection especially in a setting of recurrent exposure.