Analysis of a successful HCV-specific CD8+ T cell response in patients with recurrent HCV-infection after orthotopic liver transplantation
✍ Scribed by Norbert Hubert Gruener; Maria-Christina Jung; Axel Ulsenheimer; Joern Tilman Gerlach; Reinhart Zachoval; Helmut Michael Diepolder; Gustavo Baretton; Rolf Schauer; Gerd Rudolf Pape; Carl Albrecht Schirren
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 158 KB
- Volume
- 10
- Category
- Article
- ISSN
- 1527-6465
- DOI
- 10.1002/lt.20300
No coin nor oath required. For personal study only.
✦ Synopsis
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)-alpha / 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-gamma 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.