title: Human herpesvirus 6 impairs differentiation of monocytes to dendritic cells.
abstract: OBJECTIVE
  Monocyte-derived dendritic cells (DCs) play important roles in the immune response against infections and malignancies. Human herpesvirus 6 (HHV-6) infects monocytes and is reactivated in immunodeficient patients. To clarify the mechanisms of HHV-6-induced immunodeficiency, we investigated the effect of HHV-6 infection on differentiation of monocytes to DCs.
  
  
  METHODS
  Monocytes were inoculated with or without HHV-6 and then allowed to differentiate to myeloid DCs in culture medium containing granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4. The expression of cell surface molecules on DCs and the capacity of the DCs for antigen capture were examined by flow cytometric analysis. Alteration of antigen-presenting capacity induced by HHV-6 infection was examined.
  
  
  RESULTS
  The morphology of HHV-6-infected monocyte-derived DCs was distinctly different from that of the DCs derived from mock-infected monocytes. Although expression levels of DC-associated surface antigens, including CD80, CD83, and CD86, were significantly higher on HHV-6-infected monocyte-derived DCs than on DCs derived from mock-infected monocytes, antigen-presenting capacity was significantly lower in the former group. Addition of culture supernatant of HHV-6-infected monocytes resulted in suppression of the T-lymphocyte proliferative response, and anti-IL-10 neutralizing antibody partly inhibited this suppressive effect. The antigen-presenting capacity of DCs generated from a patient with severe HHV-6 reactivation was significantly lower than that of DCs generated from the same patient in the recovery phase.
  
  
  CONCLUSIONS
  HHV-6 infection induces immunodeficiency via impaired differentiation of DCs. These results present a new concept for the pathogenesis of HHV-6-induced immunodeficiency.
authors.affiliation: First Department of Internal Medicine, Ehime University School of Medicine Shitsukawa, Toon, Ehime, Japan.
authors.forename: Hironari
authors.initials: H
authors.lastname: Niiya
authors.forename: Jin
authors.initials: J
authors.lastname: Lei
authors.forename: Yun
authors.initials: Y
authors.lastname: Guo
authors.forename: Taichi
authors.initials: T
authors.lastname: Azuma
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yakushijin
authors.forename: Ikuya
authors.initials: I
authors.lastname: Sakai
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hato
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tohyama
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D017931:DNA Primers; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology; D005434:Flow Cytometry; D015654:Herpesvirus 6, Human / Q000502:physiology*; D009000:Monocytes / Q000166:cytology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
chemical_list: D017931:DNA Primers