title: Acute graft-versus-host disease and steroid treatment impair CD11c+ and CD123+ dendritic cell reconstitution after allogeneic peripheral blood stem cell transplantation.
abstract: Human dendritic cells (DC) comprise 2 subsets-plasmacytoid CD123(+) and myeloid CD11c(+) DC-that may have distinct roles in the regulation of immunity after allogeneic hematopoietic stem cell transplantation. In this study, we analyzed the kinetics of CD123(+) DC and CD11c(+) DC reconstitution in 31 patients who underwent transplantation with allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood (PB) stem cells from HLA-identical sibling donors after myeloablative conditioning. Lineage marker-negative HLA-DR(+) CD11c(+) CD11c(+) DC and lineage marker-negative HLA-DR(+) CD123(+) CD123(+) DC, as well as monocytes and lymphoid subsets, were enumerated in donor grafts and in the PB of patients at various time points after transplantation. Reconstitution of both CD11c(+) DC and CD123(+) DC to normal levels occurred within 6 to 12 months and was not affected by the diagnosis, preparatory regimen, or graft composition. However, PB CD11c(+) DC and CD123(+) DC counts were significantly reduced in patients with acute GVHD grade II to IV (at 1 and 3 months) and grade I (at 1 month). Patients with chronic GVHD instead showed reduced CD123(+) DC counts only 6 months after transplantation. Moreover, treatment with steroids (>0.1 mg/kg) was significantly associated with reduced PB CD11c(+) DC and CD123(+) DC counts at all time points after transplantation. In multivariate analysis, only acute GVHD affected DC reconstitution early after transplantation. These results will prompt new studies addressing whether DC reconstitution correlates with immunity against infectious agents or with graft-versus-tumor reactions after PB stem cell allotransplantation.
authors.affiliation: Research Center for Transplant Immunology, Institute of Hematology and Medical Oncology Seràgnoli, University of Bologna, Italy. arpinati@med.unibo.it
authors.forename: Mario
authors.initials: M
authors.lastname: Arpinati
authors.forename: Gabriella
authors.initials: G
authors.lastname: Chirumbolo
authors.forename: Benedetta
authors.initials: B
authors.lastname: Urbini
authors.forename: Francesca
authors.initials: F
authors.lastname: Bonifazi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bandini
authors.forename: Yogen
authors.initials: Y
authors.lastname: Saunthararajah
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zagnoli
authors.forename: Marta
authors.initials: M
authors.lastname: Stanzani
authors.forename: Sadia
authors.initials: S
authors.lastname: Falcioni
authors.forename: Giulia
authors.initials: G
authors.lastname: Perrone
authors.forename: Sante
authors.initials: S
authors.lastname: Tura
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Damiano
authors.initials: D
authors.lastname: Rondelli
mesh_terms: D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology; D039521:CD11c Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit; D007700:Kinetics; D008875:Middle Aged; D015999:Multivariate Analysis; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D016185:Receptors, Interleukin-3; D012038:Regeneration / Q000187:drug effects*; D014184:Transplantation, Homologous
chemical_list: D000305:Adrenal Cortex Hormones; D039521:CD11c Antigen; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D016185:Receptors, Interleukin-3