Reconstitution of hepatitis C virus-specific T-cell - Mediated immunity after liver transplantation

Scott J. Weston, Rachel L. Leistikow, K. Rajender Reddy, Maria Torres, Anne M Wertheimer, David M. Lewinsohn, Sunwen Chou, Michael P. Davey, Christopher Corless, Cliona O'Farrelly, David R. Nelson, Hugo R. Rosen

Research output: Contribution to journalArticle

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Abstract

Hepatitis C virus (HCV)-related liver failure is the leading indication for liver transplantation worldwide. After transplantation, virological recurrence is the rule, but the spectrum of histological injury is wide, ranging from the development of allograft cirrhosis within a few years to minimal hepatitis despite long-term follow-up. The immunological correlates of this variable natural history are poorly understood. Here, we studied the kinetics of the cellular immune responses, viral replication, and allograft histology in 24 patients who had undergone liver transplantation for HCV-related liver failure. Using direct ex vivo methodologies (i.e., interferon-gamma ELISPOT and major histocompatibility complex class I-peptide tetrameric complexes), we found that patients who experienced viral eradication after anti-viral therapy showed restoration of HCV-specific T-cell responses, whereas patients with progressive HCV recurrence that failed to respond to therapy showed declining frequencies of these viral-specific effector cells. The cytotoxic T lymphocytes that peripherally reconstituted after transplantation were clonotypically identical to those present within the recipient explant liver, defined at the level of the T-cell receptor beta chain (one epitope/one clone). Moreover, the subset of patients who spontaneously demonstrated minimal histologic recurrence had more vigorous CD4+ T-cell responses in the first 3 months, particularly targeting nonstructural proteins. We provide evidence that T-cell responses emerge after liver transplantation, and their presence correlates with improved histological and clinical outcomes. In conclusion, these results may help identify patients more likely to develop severe HCV recurrence and therefore benefit from current antiviral therapy, as well as provide a rationale for the future use of novel immunotherapeutic approaches.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalHepatology
Volume41
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

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Cellular Immunity
Hepacivirus
Liver Transplantation
T-Lymphocytes
Recurrence
Liver Failure
Allografts
Transplantation
Antigen Receptors, T-Cell, alpha-beta
Enzyme-Linked Immunospot Assay
Cytotoxic T-Lymphocytes
Protein Transport
Major Histocompatibility Complex
Natural History
Hepatitis
Interferon-gamma
Antiviral Agents
Epitopes
Histology
Fibrosis

ASJC Scopus subject areas

  • Hepatology

Cite this

Weston, S. J., Leistikow, R. L., Reddy, K. R., Torres, M., Wertheimer, A. M., Lewinsohn, D. M., ... Rosen, H. R. (2005). Reconstitution of hepatitis C virus-specific T-cell - Mediated immunity after liver transplantation. Hepatology, 41(1), 72-81. https://doi.org/10.1002/hep.20507

Reconstitution of hepatitis C virus-specific T-cell - Mediated immunity after liver transplantation. / Weston, Scott J.; Leistikow, Rachel L.; Reddy, K. Rajender; Torres, Maria; Wertheimer, Anne M; Lewinsohn, David M.; Chou, Sunwen; Davey, Michael P.; Corless, Christopher; O'Farrelly, Cliona; Nelson, David R.; Rosen, Hugo R.

In: Hepatology, Vol. 41, No. 1, 01.2005, p. 72-81.

Research output: Contribution to journalArticle

Weston, SJ, Leistikow, RL, Reddy, KR, Torres, M, Wertheimer, AM, Lewinsohn, DM, Chou, S, Davey, MP, Corless, C, O'Farrelly, C, Nelson, DR & Rosen, HR 2005, 'Reconstitution of hepatitis C virus-specific T-cell - Mediated immunity after liver transplantation', Hepatology, vol. 41, no. 1, pp. 72-81. https://doi.org/10.1002/hep.20507
Weston, Scott J. ; Leistikow, Rachel L. ; Reddy, K. Rajender ; Torres, Maria ; Wertheimer, Anne M ; Lewinsohn, David M. ; Chou, Sunwen ; Davey, Michael P. ; Corless, Christopher ; O'Farrelly, Cliona ; Nelson, David R. ; Rosen, Hugo R. / Reconstitution of hepatitis C virus-specific T-cell - Mediated immunity after liver transplantation. In: Hepatology. 2005 ; Vol. 41, No. 1. pp. 72-81.
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