title: Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders.
abstract: As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein-Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B- and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B- and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell post-transplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell post-transplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of ≤0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio ≤0.4 (P = 0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.
authors.affiliation: Department of Histopathology, Hammersmith Hospital, Imperial College, London, UK.
authors.forename: Hazem A H
authors.initials: HA
authors.lastname: Ibrahim
authors.forename: Lia P
authors.initials: LP
authors.lastname: Menasce
authors.forename: Sabine
authors.initials: S
authors.lastname: Pomplun
authors.forename: Margaret
authors.initials: M
authors.lastname: Burke
authors.forename: Mark
authors.initials: M
authors.lastname: Bower
authors.forename: Kikkeri N
authors.initials: KN
authors.lastname: Naresh
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D046888:Tissue Array Analysis