title: Spontaneous outgrowth of EBV-transformed B-cells reflects EBV-specific immunity in vivo; a useful tool in the follow-up of EBV-driven immunoproliferative disorders in allograft recipients.
abstract: During immunosuppressive medication, Epstein-Barr virus (EBV) infection is associated with a risk of developing posttransplant lymphoproliferative disease (PTLD). The appropriateness of a spontaneous EBV B-cell transformation (SET) assay as a monitor of EBV-specific immunity was evaluated to investigate if it safely allows reducing immunosuppressive medication, thereby decreasing the risk of developing PTLD. PBMC were isolated longitudinally from 20 pediatric renal allograft recipients treated with prednisone and cyclosporine combined with either azathioprine or mycophenolate mofetil. Most significantly, EBV-peptide-specific CD8+ T cells were detectable in the blood of patients with negative SET assays, coinciding with significantly lower EBV loads, whereas these cells were less frequent in the blood of patients with positive SET assays. Reducing the levels of immunosuppression resulted in normalization of the SET assays. Therefore, the SET assay is a reflection of the interaction between viral replication, transformation of B cells, and EBV-specific immunity in vivo and hence a valuable screening test for EBV-driven lymphoproliferative phenomena in allograft recipients.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.t.vossen@amc.uva.nl
authors.forename: Mireille T M
authors.initials: MT
authors.lastname: Vossen
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Gent
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Davin
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baars
authors.forename: Pauline M E
authors.initials: PM
authors.lastname: Wertheim-van Dillen
authors.forename: Jan F L
authors.initials: JF
authors.lastname: Weel
authors.forename: Marijke T L
authors.initials: MT
authors.lastname: Roos
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Jaap
authors.initials: J
authors.lastname: Groothoff
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
mesh_terms: D015703:Antigens, CD / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002472:Cell Transformation, Viral / Q000276:immunology*; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007160:Immunoproliferative Disorders / Q000821:virology*; D016030:Kidney Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D011183:Postoperative Complications / Q000276:immunology / Q000821:virology; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D015703:Antigens, CD