Analysis of a successful HCV‐specific CD8+ T cell response in patients with recurrent HCV‐infection after orthotopic liver transplantation

Virus‐specific CD8+ T cells play a major role in antiviral immune defenses; their significance in the transplant setting, however, is unclear. In the present study, we asked whether hepatitis C virus (HCV)‐specific CD8+ T cells were detectable in the presence of an immunosuppressive treatment and whether the HCV‐specific CD8+ T cell response correlates with treatment outcome in patients who receive interferon (IFN)‐α / ribavirin therapy after orthotopic liver transplantation (OLTx). Liver‐ and blood‐derived T cell lines of 21 patients after OLTx were studied before, at the end of, and after antiviral treatment. Virus‐specific IFN‐γ production in response to a panel of previously identified HCV‐specific epitopes restricted by the human leukocyte antigen (HLA) class I molecules A2, A3, B7, B35, and B44 of structural and nonstructural HCV protein was determined by enzyme‐linked immunospot (ELISPOT) assay. Before treatment, only low numbers of HCV‐specific CD8+ T cells were detectable. In 6 patients with a sustained virological response, a significant, multispecific, and sustained CD8+ T cell response was detectable, which was mainly found in the peripheral blood. Nonresponders and transient responders showed undetectable, weak, or transient HCV‐specific CD8+ T cell responses. (Sustained responders vs. transient and nonresponders: Wilcoxon rank‐signed test; P < .01). In conclusion, our data indicate that despite immunosuppression, HCV‐specific CD8+ T cells are detectable in patients with recurrent HCV infection after OLTx and that a significant, multispecific, and long‐lasting HCV‐specific CD8+ T cell response contributes to viral elimination. (Liver Transpl 2004;10:1487–1496.)