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.