title: Factors affecting human T cell engraftment, trafficking, and associated xenogeneic graft-vs-host disease in NOD/SCID beta2mnull mice.
abstract: OBJECTIVE
  Graft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Models of immunodeficient mice that consistently and efficiently reconstitute with xenoreactive human T cells would be a valuable tool for the in vivo study of GVHD, as well as other human immune responses.
  
  
  METHODS
  We developed a consistent and sensitive model of human GVHD by retro-orbitally injecting purified human T cells into sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID)-beta2m(null) recipients. In addition, we characterized for the first time the trafficking patterns and expansion profiles of xenoreactive human T cells in NOD/SCID-beta2m(null) recipients using in vivo bioluminescence imaging.
  
  
  RESULTS
  All NOD/SCID-beta2m(null) mice conditioned with 300 cGy total body irradiation and injected with 1 x 10(7) human T cells exhibited human T-cell engraftment, activation, and expansion, with infiltration of multiple target tissues and a subsequent >20% loss of pretransplantation body weight. Importantly, histological examination of the GVHD target tissues revealed changes consistent with human GVHD. Furthermore, we also showed by in vivo bioluminescence imaging that development of lethal GVHD in the NOD/SCID-beta2m(null) recipients was dependent upon the initial retention and early expansion of human T cells in the retro-orbital sinus cavity.
  
  
  CONCLUSIONS
  Our NOD/SCID-beta2m(null) mouse model provides a system to study the pathophysiology of acute GVHD induced by human T cells and aids in development of more effective therapies for human GVHD.
authors.affiliation: Division of Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Bruno
authors.initials: B
authors.lastname: Nervi
authors.forename: Michael P
authors.initials: MP
authors.lastname: Rettig
authors.forename: Julie K
authors.initials: JK
authors.lastname: Ritchey
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bauer
authors.forename: Jon
authors.initials: J
authors.lastname: Walker
authors.forename: Mark L
authors.initials: ML
authors.lastname: Bonyhadi
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Berenson
authors.forename: Julie L
authors.initials: JL
authors.lastname: Prior
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: Jan A
authors.initials: JA
authors.lastname: Nolta
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006086:Graft vs Host Disease; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000166:cytology*; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D001613:beta 2-Microglobulin