title: Decreased IL-7 signaling in T cells from patients with PTLD after allogeneic HSCT.
abstract: Interleukin (IL)-7, a nonredundant cytokine for B and T cells, plays a central role in cell survival and immune memory formation. Peripheral blood mononuclear cells (PBMCs) from 7 patients after hematopoietic stem cell transplantation (HSCT) diagnosed with posttransplantation lymphoproliferative disease (PTLD) and from 10 Epstein-Barr virus (EBV) polymerase chain reaction-positive HSCT patients (controls) were evaluated for IL-7- and IL-2 induced Stat5 phosphorylation in CD4+ and CD8+ T cells. PBMCs from PTLD+ and control patients exhibited detectable EBV specific CD8+ T cells defined by tetramer analysis. CD4+ and CD8+ T cells from patients with PTLD showed statistically significant reduction in responsiveness to IL-7 compared with PBMCs obtained from controls defined by Stat5 phosphorylation. CD20+ B cells from patients with PTLD and from some EBV+ polymerase chain reaction control individuals exhibited IL-7R expression. Dysregulated immune surveillance, reflected by deficient Stat5 phosphorylation, may facilitate PTLD development despite the presence of EBV-reactive CD8+ T cells. Reduced IL-7 responsiveness will aid to monitor patients after HSCT for increased risk to develop EBV-associated PTLD.
authors.affiliation: Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Omar
authors.forename: Raija
authors.initials: R
authors.lastname: Ahmed
authors.forename: Lalit
authors.initials: L
authors.lastname: Rane
authors.forename: Andreas
authors.initials: A
authors.lastname: Björklund
authors.forename: Asa
authors.initials: A
authors.lastname: Gustafsson-Jernberg
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D015851:Interleukin-7 / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000503:physiopathology*; D010766:Phosphorylation / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000939:Epitopes; D015851:Interleukin-7; D050799:STAT5 Transcription Factor