Expansion of EBNA1-specific effector T cells in posttransplantation lymphoproliferative disorders

Jones, Kimberley, Nourse, Jamie P., Morrison, Leanne, Nguyen-Van, Do, Moss, Denis J., Burrows, Scott R. and Gandhi, Maher K. (2010) Expansion of EBNA1-specific effector T cells in posttransplantation lymphoproliferative disorders. Blood, 116 13: 2245-2252. doi:10.1182/blood-2010-03-274076

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Author Jones, Kimberley
Nourse, Jamie P.
Morrison, Leanne
Nguyen-Van, Do
Moss, Denis J.
Burrows, Scott R.
Gandhi, Maher K.
Title Expansion of EBNA1-specific effector T cells in posttransplantation lymphoproliferative disorders
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2010-09-30
Year available 2010
Sub-type Article (original research)
DOI 10.1182/blood-2010-03-274076
Volume 116
Issue 13
Start page 2245
End page 2252
Total pages 8
Editor Cynthia E. Dunbar
Place of publication Washington, DC, USA
Publisher American Society of Hematology
Language eng
Formatted abstract
Immunosuppression resulting in impaired Epstein-Barr virus (EBV)–specific T-cell immunity is involved in the pathogenesis of EBV-positive post-transplantation lymphoproliferative disorder (EBV+ PTLD). Restoration of EBV-specific T-cell immunity by adoptive immunotherapy can induce remission. EBV-nuclear antigen-1 (EBNA1) is unique in being expressed in all cases of EBV+ PTLD. Recent data demonstrate that EBNA1 is not immunologically silent and can be exploited as a T-cell target. There are no data on EBNA1-specific T cells in PTLD. EBNA1-specific T cells capable of proliferation, interferon-γ release, and CD107a/b degranulation were assayed in 14 EBV+ PTLD diagnostic blood samples and 19 healthy controls. EBNA1-specific CD4+ T cells predominated and were expanded in 10 of 14 patients and 19 of 19 controls. Although human leukocyte antigen class I alleles influenced the magnitude of the response, EBNA1-specific CD8+ effector T cells were successfully generated in 9 of 14 EBV+ PTLD patients and 16 of 19 controls. The majority of PTLD patients had a polymorphism in an EBNA1 epitope, and T-cell recognition was greatly enhanced when EBNA1 peptides derived from the polymorphic epitope were used. These results indicate that EBNA1-specific T cells should be included in adoptive immunotherapy for PTLD. Furthermore, expansion protocols should use antigenic sequences from relevant EBV strains.
© 2010 by The American Society of Hematology
Keyword Epstein-Barr-virus
Nuclear antigen EBNA1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 21 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 28 Mar 2011, 20:22:46 EST by Debbie Banks on behalf of Medicine - Princess Alexandra Hospital