The Role of Virus-Specific Cd8+ Cells in Liver Damage and Viral Control during Persistent Hepatitis B Virus Infection (original) (raw)
Article| April 10 2000
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
bDepartment of Sexually Transmitted Diseases, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Search for other works by this author on:
dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
bDepartment of Sexually Transmitted Diseases, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
eCromwell Hospital, London SW5 0TU, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
Search for other works by this author on:
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Search for other works by this author on:
Mala K. Maini
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
bDepartment of Sexually Transmitted Diseases, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Carolina Boni
cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
Chun Kyon Lee
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Juan R. Larrubia
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Stephanie Reignat
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Graham S. Ogg
dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Abigail S. King
dMolecular Immunology Group, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
Jethro Herberg
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Richard Gilson
bDepartment of Sexually Transmitted Diseases, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Akeem Alisa
eCromwell Hospital, London SW5 0TU, United Kingdom
Roger Williams
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Diego Vergani
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Nikolai V. Naoumov
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Carlo Ferrari
cLaboratorio Immunopatologia Virale, Ospedale di Parma, 43100 Parma, Italy
Antonio Bertoletti
aInstitute of Hepatology, University College London and University College of London Hospitals, London WC1E 6HX, United Kingdom
Abbreviations used in this paper: ALT, alanine transaminase; HBc, HBV core; HBe, HBV e; HBs, HBV surface; HBV, hepatitis B virus; HCV, hepatitis C virus; Tc 18–27, core 18–27 HLA-A2 tetrameric complex; Te 335–343, envelope 335–343 HLA-A2 tetrameric complex; Tp 575–583, polymerase 575–583 HLA-A2 tetrameric complex.
Received: October 25 1999
Revision Requested: January 17 2000
Accepted: January 27 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (8): 1269–1280.
Received:
October 25 1999
Revision Requested:
January 17 2000
Accepted:
January 27 2000
Citation
Mala K. Maini, Carolina Boni, Chun Kyon Lee, Juan R. Larrubia, Stephanie Reignat, Graham S. Ogg, Abigail S. King, Jethro Herberg, Richard Gilson, Akeem Alisa, Roger Williams, Diego Vergani, Nikolai V. Naoumov, Carlo Ferrari, Antonio Bertoletti; The Role of Virus-Specific Cd8+ Cells in Liver Damage and Viral Control during Persistent Hepatitis B Virus Infection. _J Exp Med 17 April 2000; 191 (8): 1269–1280. doi: https://doi.org/10.1084/jem.191.8.1269
Download citation file:
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.
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.
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
You do not currently have access to this content.
Sign in
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Username (Note: This may be your email address.) ?
Password
Could not validate captcha. Please try again.
17,591 Views
703 Web of Science