title: Expansion and activation kinetics of immune cells during early phase of GVHD in mouse model based on chemotherapy conditioning.
abstract: In the present paper, we have investigated early pathophysiological events in graft-versus-host disease (GVHD), a major complication to hematopoietic stem cell transplantation (HSCT). BLLB/c female mice conditioned with busulfan/cyclophosphamide (Bu-Cy) were transplanted with allogeneic male C57BL/6. Control group consisted of syngeneic transplanted Balb/c mice. In allogeneic settings, significant expansion and maturation of donor dendritic cells (DCs) were observed at day +3, while donor T-cells CD8+ were increased at day +5 (230%) compared to syngeneic HSCT. Highest levels of inflammatory cytokines IL-2, IFN-gamma, and TNF-alfa at day +5 matched T-cell activation. Concomitantly naïve T-cells gain effecr-memory phenotype and migrated from spleen to peripheral lymphoid organs. Thus, in the very early phase of GHVD following Bu-Cy conditioning donor, DCs play an important role in the activation of donor T cells. Subsequently, donor naïve T-cells gain effector-memory phenotype and initiate GVHD.
authors.affiliation: Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institutet, 141 86 Stockholm, Sweden. behnam.sadeghi@ki.se
authors.forename: Behnam
authors.initials: B
authors.lastname: Sadeghi
authors.forename: Suleiman
authors.initials: S
authors.lastname: Al-Hashmi
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Hassan
authors.forename: Bjorn
authors.initials: B
authors.lastname: Rozell
authors.forename: Hernan
authors.initials: H
authors.lastname: Concha
authors.forename: Carin
authors.initials: C
authors.lastname: Lundmark
authors.forename: Kjell-Olov
authors.initials: KO
authors.lastname: Grönvik
authors.forename: Manuchehr
authors.initials: M
authors.lastname: Abedi-Valugerdi
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002066:Busulfan / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013997:Time Factors; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003520:Cyclophosphamide; D002066:Busulfan