title: Clinical significance of cloned expansion and CD5 down-regulation in Epstein-Barr Virus (EBV)-infected CD8+ T lymphocytes in EBV-associated hemophagocytic lymphohistiocytosis.
abstract: Epstein-Barr virus (EBV) is the pathogen that most commonly triggers infection-associated hemophagocytic lymphohistiocytosis (HLH) and ectopically infects CD8(+) T cells in EBV-associated HLH (EBV-HLH). We recently described an EBV-HLH patient who had a clonally expanded population of EBV-infected CD8(+) T cells with CD5 down-regulation. To determine whether this finding could serve as a useful marker for EBV-HLH, we investigated 5 additional patients. We found a significant increase in the subpopulation of CD8(+) T cells with CD5 down-regulation and bright human leukocyte antigen (HLA)-DR expression in all patients with EBV-HLH but not in patients with infectious mononucleosis or in control subjects. Such T cells were frequently found to be larger cells that stained positive for a specific T cell receptor VB. We also demonstrated that those cells were the major cellular target of EBV, and their numbers progressively declined in parallel with the serum ferritin levels. All together, our findings reveal the immunophenotypic characteristics of EBV-infected CD8(+) T cells and may provide a valuable tool for the diagnosis of EBV-HLH.
authors.affiliation: Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Toga
authors.forename: Taizo
authors.initials: T
authors.lastname: Wada
authors.forename: Yasuhisa
authors.initials: Y
authors.lastname: Sakakibara
authors.forename: Shintaro
authors.initials: S
authors.lastname: Mase
authors.forename: Raita
authors.initials: R
authors.lastname: Araki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tone
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toma
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Ryu
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamura
authors.forename: Naonori
authors.initials: N
authors.lastname: Nishida
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Taneichi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
mesh_terms: D018956:CD5 Antigens / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D051359:Lymphohistiocytosis, Hemophagocytic / Q000276:immunology* / Q000821:virology*; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D018956:CD5 Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell