title: Histological assessment of the sclerotic graft-versus-host response in the humanized RAG2-/-γc-/- mouse model.
abstract: Graft-versus-host disease (GVHD) remains a frequently occurring and difficult-to-treat complication in human allogeneic stem cell transplantation. Murine transplantation models are often used to study and understand the complex pathogenesis of GVHD and to explore new treatment strategies. Although GVHD kinetics may differ in murine and human models, adequate models are essential for identification of the crucial factors responsible for the major pathology in GVHD. We present a detailed description of the specific histological features of a graft-versus-host-induced fibrotic response in xenogeneic RAG2(-/-)γc(-/-) mice after total body irradiation and injection with human peripheral blood mononuclear cells. We describe the full morphological features of this reaction, including a detailed analysis of the specific tissue infiltration patterns of the human peripheral blood mononuclear cells. Our data show the development of fibrosis, predominantly near blood vessels, and reveal different cell populations and specific cell migration patterns in the affected organs. The combination of immunohistochemical cell characterization and mRNA expression analysis of both human (donor)- and murine (host)-derived cytokines reveals an interaction between host tissues and donor-derived cells in an entangled cytokine profile, in which both donor- and host-derived cytokines contribute to the formation of fibrosis.
authors.affiliation: Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht, The Netherlands.
authors.forename: Marieke C H
authors.initials: MC
authors.lastname: Hogenes
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Dorp
authors.forename: Joyce
authors.initials: J
authors.lastname: van Kuik
authors.forename: Filipa R P
authors.initials: FR
authors.lastname: Monteiro
authors.forename: Natalie
authors.initials: N
authors.lastname: ter Hoeve
authors.forename: Marijke R
authors.initials: MR
authors.lastname: van Dijk
authors.forename: Anton C
authors.initials: AC
authors.lastname: Martens
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000276:immunology / Q000473:pathology*; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012598:Sclerosis; D014183:Transplantation, Heterologous; D014916:Whole-Body Irradiation
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; C499308:Rag2 protein, mouse