T CD8 response in diverse outcomes of recurrent exposure to hepatitis C virus

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Abstract
To analyse the immune correlates in a setting of recurrent exposure to hepatitis C virus (HCV), we studied TCD8 responses in injecting drug users (IDUs) with different disease outcomes. Ex vivo HCV‐specific TCD8 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 TCD8 cells in age and HLA‐matched IDUs demonstrated that HCV clearance and protection from reinfection correlated with HCV‐specific TCD8 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 TCD8 cells determined ex vivo. While validating the importance of multifunctional TCD8 in mediating protection in IDUs with recurrent exposure to HCV our findings highlight that the magnitude and/or breadth of HCV‐specific TCD8 determined in ex vivo ELISPOT may not be the sole determinant of protection especially in a setting of recurrent exposure.
Funding Information
  • National Health and Medical Research Council (331312, 208981)