The Role of Virus-Specific Cd8+ Cells in Liver Damage and Viral Control during Persistent Hepatitis B Virus Infection
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- Mala K. Maini
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Carolina Boni
- cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
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- Chun Kyon Lee
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Juan R. Larrubia
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Stephanie Reignat
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Graham S. Ogg
- dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
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- Abigail S. King
- dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
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- Jethro Herberg
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Richard Gilson
- bDepartment of Sexually Transmitted Diseases, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Akeem Alisa
- eCromwell Hospital, London SW5 0TU, United Kingdom
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- Roger Williams
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Diego Vergani
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Nikolai V. Naoumov
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
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- Carlo Ferrari
- cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
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- Antonio Bertoletti
- aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
抄録
<jats:p>Hepatitis B virus (HBV) is a noncytopathic virus, and the recognition of infected hepatocytes by HBV-specific CD8 cells has been assumed to be the central mechanism causing both liver damage and virus control. To understand the role of cytotoxic T cells in the pathogenesis of HBV infection, we used functional assays that require T cell expansion in vitro and human histocompatibility leukocyte antigen (HLA)-peptide tetramers that allow direct ex vivo quantification of circulating and liver-infiltrating HBV-specific CD8 cells. Two groups of patients with persistent HBV infection were studied: one without liver inflammation and HBV replication, the other with liver inflammation and a high level of HBV replication. Contrary to expectation, a high frequency of intrahepatic HBV-specific CD8 cells was found in the absence of hepatic immunopathology. In contrast, virus-specific T cells were more diluted among liver infiltrates in viremic patients, but their absolute number was similar because of the massive cellular infiltration. Furthermore, inhibition of HBV replication was associated with the presence of a circulating reservoir of CD8+ cells able to expand after specific virus recognition that was not detectable in highly viremic patients with liver inflammation.</jats:p> <jats:p>These results show that in the presence of an effective HBV-specific CD8 response, inhibition of virus replication can be independent of liver damage. When the HBV-specific CD8 response is unable to control virus replication, it may contribute to liver pathology not only directly but by causing the recruitment of nonvirus-specific T cells.</jats:p>
収録刊行物
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- The Journal of Experimental Medicine
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The Journal of Experimental Medicine 191 (8), 1269-1280, 2000-04-10
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1361418519734019456
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- NII論文ID
- 30017415238
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- ISSN
- 15409538
- 00221007
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