HCV-specific immunosuppression

Abstract

Hepatitis C virus (HCV) infects roughly 170 million people worldwide and is maintained as a chronic infection in nearly 80% of those exposed to the virus. It is believed that a strong antiviral T-cell response might be beneficial in resolving this infection, and a recent study by Gruener et al.1xSustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. Gruener, N.H. et al. J. Virol. 2001; 75: 5550–5558Crossref | PubMed | Scopus (373)See all References1 set out to determine the antiviral efficacy of HCV-specific T-cell responses. Intriguingly, they found that HCV-specific CD8+ T cells [identified using peptide–major histocompatibility complex (MHC) class I tetramers] were dysfunctional, and mostly unable to perform typical immune functions such as the synthesis of inflammatory cytokines or the lysis of infected cells. By contrast, the CD8+ T-cell response of HCV-infected patients against other chronic or latent viruses such as Epstein–Barr virus or cytomegalovirus were relatively unaffected, as these cells were able to produce antiviral cytokines directly ex vivo following stimulation with virus-specific peptides or mitogenic stimulation with phorbol-12-myristate-13-acetate (PMA) and ionomycin. Together, these results indicate that HCV-specific immunosuppression of CD8+ T-cell responses could be a contributing factor in the persistence of HCV infection.