title: Expansion of EBNA1-specific effector T cells in posttransplantation lymphoproliferative disorders.
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.
authors.affiliation: Clinical Immunohaematology Laboratory and Australian Centre for Vaccine Development, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, QLD 4006, Australia.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Jones
authors.forename: Jamie P
authors.initials: JP
authors.lastname: Nourse
authors.forename: Leanne
authors.initials: L
authors.lastname: Morrison
authors.forename: Do
authors.initials: D
authors.lastname: Nguyen-Van
authors.forename: Denis J
authors.initials: DJ
authors.lastname: Moss
authors.forename: Scott R
authors.initials: SR
authors.lastname: Burrows
authors.forename: Maher K
authors.initials: MK
authors.lastname: Gandhi
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D002648:Child; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000276:immunology*; D005260:Female; D015797:HLA-B35 Antigen / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000276:immunology / Q000628:therapy* / Q000821:virology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D052119:Lysosomal-Associated Membrane Protein 2 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D019737:Transplants / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D015797:HLA-B35 Antigen; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D007371:Interferon-gamma; C417029:EBV-encoded nuclear antigen 1