Plasmacytoid dendritic cell reconstitution following bone marrow transplantation: subnormal recovery and functional deficit of IFN-alpha/beta production in response to herpes simplex virus.
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.
Giraud
Sebastien
S
INSERM U131, Hôpital Antoine Béclère, Clamart, France.
Dhedin
Nathalie
N
Gary-Gouy
Hélène
H
Lebon
Pierre
P
Vernant
Jean-Paul
JP
Dalloul
Ali
A
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
D007166:Immunosuppressive Agents; D007370:Interferon Type I