title: Impact of donor hematopoietic cells mobilized with G-CSF and plerixafor on murine acute graft-versus-host-disease.
abstract: OBJECTIVE
  This study aimed to characterize the immune effectors contained in the grafts from donor mice mobilized by granulocyte colony-stimulating factor (G-CSF) and plerixafor and to evaluate their impact on the development of acute graft-versus-host-disease (aGVHD).
  
  
  METHODS
  Mobilization was done with G-CSF alone or G-CSF plus plerixafor (G+P).
  
  
  RESULTS
  In grafts collected after G+P mobilization, we observed a significantly higher proportion of c-kit(+)Sca-1(+) hematopoietic stem cells compared with G-CSF. A significant increase in the percentage of plasmacytoid dendritic cells was detected in the G+P graft compared with G-CSF graft. We also studied the ability of stem cell grafts mobilized with G+P to induce GVHD in a mouse model. We observed higher mortality (P < 0.001) associated with increased aGVHD clinical score (P < 0.0001) as well as higher pathology score in the intestine of mice receiving G+P as compared with G-CSF grafts (P < 0.001). Moreover, the exacerbated aGVHD severity was associated with upregulation of CCR6 expression on both CD4(+) and CD8(+) T cells from the G+P grafts, as well as on T cells from mice transplanted with G+P grafts.
  
  
  CONCLUSIONS
  In conclusion, we showed that grafts mobilized with G+P exhibited functional features different from those mobilized with G-CSF alone, which increase the severity of aGVHD in the recipients.
authors: Institut de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)1098, Besançon, France; Université de Franche-Comté, Besançon, F-25000, France; Etablissement Français du Sang Bourgogne Franche-Comté, Besançon Cedex, France.
authors: Jessy
authors: J
authors: Arbez
authors: Institut de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)1098, Besançon, France; Université de Franche-Comté, Besançon, F-25000, France; Etablissement Français du Sang Bourgogne Franche-Comté, Besançon Cedex, France.
authors: Philippe
authors: P
authors: Saas
authors: Institut de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)1098, Besançon, France; Université de Franche-Comté, Besançon, F-25000, France; Etablissement Français du Sang Bourgogne Franche-Comté, Besançon Cedex, France.
authors: Baptiste
authors: B
authors: Lamarthée
authors: Service d'Hématologie Clinique, Centre Hospitalier Universitaire and Université de Nantes, France; INSERM CRNCA UMR892, Nantes, France.
authors: Florent
authors: F
authors: Malard
authors: Institut de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)1098, Besançon, France; Université de Franche-Comté, Besançon, F-25000, France; Etablissement Français du Sang Bourgogne Franche-Comté, Besançon Cedex, France.
authors: Mélanie
authors: M
authors: Couturier
authors: Service d'Hématologie Clinique et de Thérapie Cellulaire, Hôpital Saint-Antoine, Assistance Publique des Hôpitaux de Paris, Paris, France; INSERM UMRS938, Centre de Recherche Saint-Antoine, Paris, France.
authors: Mohamad
authors: M
authors: Mohty
authors: Institut de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR)1098, Besançon, France; Université de Franche-Comté, Besançon, F-25000, France; Etablissement Français du Sang Bourgogne Franche-Comté, Besançon Cedex, France. Electronic address: beatrice.gaugler@inserm.fr.
authors: Béatrice
authors: B
authors: Gaugler
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001596:Benzylamines; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000080027:Cyclams; D003713:Dendritic Cells / Q000378:metabolism; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D013154:Spleen / Q000166:cytology
chemical_list: D000950:Antigens, Ly; D001596:Benzylamines; C498126:CCR6 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D054399:Receptors, CCR6; D016179:Granulocyte Colony-Stimulating Factor; D019009:Proto-Oncogene Proteins c-kit; C088327:plerixafor
keywords: acute GVHD; dendritic cells; immune effectors; mobilization; peripheral blood stem cells; plerixafor