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Sustained and focused hepatitis B virus nucleocapsid-specific T-cell immunity in liver transplant recipients compared to individuals with chronic and self-limited hepatitis B virus infection.

Abstract
Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT) is associated with poor graft- and patient-survival. Treatment with HBV-specific immunoglobulins (HBIG) in combination with nucleos(t)ide analogs is effective in preventing HBV reinfection of the graft and improving OLT outcome. However, the role of HBV-specific cellular immunity in viral containment in immune suppressed patients in general and in OLT recipients in particular is unclear. To test whether or not OLT recipients maintain robust HBV-specific cellular immunity, the cellular immune response against HBV was assessed in 15 OLT recipients and 27 individuals with chronic and 24 subjects with self-limited HBV infection, respectively; using an overlapping peptide set spanning the viral nucleocapsid- and envelope-protein sequences. The data demonstrate that OLT recipients mounted fewer but stronger clusters of differentiation (CD)8 T cell responses than subjects with self-limited HBV infection and showed a preferential targeting of the nucleocapsid antigen. This focused response pattern was similar to responses seen in chronically infected subjects with undetectable viremia, but significantly different from patients who presented with elevated HBV viremia and who mounted mainly immune responses against the envelope protein. In conclusion, virus-specific CD4 T cell-mediated responses were only detected in subjects with self-limited HBV infection. Thus, the profile of the cellular immunity against HBV was in immune suppressed patients similar to subjects with chronic HBV infection with suppressed HBV-DNA.
AuthorsFlorian Bihl, Elisabetta Loggi, John V Chisholm 3rd, Maurizio Biselli, Maria C Morelli, Carmela Cursaro, Norah A Terrault, Mauro Bernardi, Antonio Bertoletti, Pietro Andreone, Christian Brander
JournalLiver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society (Liver Transpl) Vol. 14 Issue 4 Pg. 478-85 (Apr 2008) ISSN: 1527-6473 [Electronic] United States
PMID18324666 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Copyright(c) 2008 AASLD.
Chemical References
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Immunosuppressive Agents
  • Cyclosporine
  • Tacrolimus
Topics
  • Antibody Specificity
  • Cyclosporine (therapeutic use)
  • DNA, Viral (analysis)
  • Hepatitis B (immunology)
  • Hepatitis B Surface Antigens (blood)
  • Hepatitis B e Antigens (blood)
  • Hepatitis B virus (genetics, immunology)
  • Hepatitis B, Chronic (immunology)
  • Humans
  • Immunosuppressive Agents (therapeutic use)
  • Liver Transplantation (immunology)
  • Lymphocytes (immunology)
  • Nucleocapsid (immunology)
  • Recurrence
  • T-Lymphocytes (immunology)
  • Tacrolimus (therapeutic use)
  • Viral Load

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