Clinical significance of cloned expansion and CD5 down-regulation in Epstein-Barr Virus (EBV)-infected CD8+ T lymphocytes in EBV-associated hemophagocytic lymphohistiocytosis.
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.
Toga
Akiko
A
Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Wada
Taizo
T
Sakakibara
Yasuhisa
Y
Mase
Shintaro
S
Araki
Raita
R
Tone
Yumi
Y
Toma
Tomoko
T
Kurokawa
Toshiro
T
Yanagisawa
Ryu
R
Tamura
Kentaro
K
Nishida
Naonori
N
Taneichi
Hiromichi
H
Kanegane
Hirokazu
H
Yachie
Akihiro
A
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
D018956:CD5 Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell