title: Plasmacytoid dendritic cell reconstitution following bone marrow transplantation: subnormal recovery and functional deficit of IFN-alpha/beta production in response to herpes simplex virus.
abstract: Infections with herpesviruses were frequent after bone marrow transplantation (BMT) before the preventive use of antiviral drugs, suggesting a deficit of innate immunity. A retrospective phenotypical and functional study was carried out on 25 patients 1-36 months after allogeneic BMT. Leukocyte counts followed a normal reconstitution, including natural killer (NK) cells and monocytes. Plasmacytoid dendritic cell (PDC) counts increased steadily, although they remained below normal values after 2 years. Most patients produced less interferon- alpha/beta (IFN-alphabeta) in vitro than healthy controls after infection with herpes simplex virus type 1 (HSV-1), whereas they responded normally to Sendai virus (SV). In addition, 6 patients had biologic signs of infection with herpesviruses, confirming a specific immunologic deficit against these viruses. IFN production was not correlated to PDC counts or to the occurrence of graft-versus-host disease (GVHD). Because all patients were under immunosuppressive treatment, we investigated the effect of drugs on IFN production by mononuclear cells. Glucocorticoids and cyclosporine A inhibited IFN production by infected leukocytes, with a predominant action on HSV-1-infected PDC. The inability of transplanted patients to mount an efficient immune response to herpesviruses may be partly related to drug toxicity toward cells of the innate immune system.
authors.affiliation: INSERM U131, Hôpital Antoine Béclère, Clamart, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Giraud
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.forename: Hélène
authors.initials: H
authors.lastname: Gary-Gouy
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Ali
authors.initials: A
authors.lastname: Dalloul
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology*; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D007113:Immunity, Innate; D007166:Immunosuppressive Agents / Q000009:adverse effects; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000096:biosynthesis*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D029082:Sendai virus / Q000276:immunology / Q000472:pathogenicity; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D007370:Interferon Type I