title: Reperfusion injury intensifies the adaptive human T cell alloresponse in a human-mouse chimeric artery model.
abstract: OBJECTIVE
  Perioperative nonimmune injuries to an allograft can decrease graft survival. We have developed a model for studying this process using human materials.
  
  
  RESULTS
  Human artery segments were transplanted as infrarenal aortic interposition grafts into an immunodeficient mouse host, allowed to "heal in" for 30 days, and then retransplanted into a second mouse host. To induce a reperfusion injury, the healed-in artery segments were incubated for 3 hours under hypoxic conditions ex vivo before retransplantation. To induce immunologic rejection, the animals receiving the retransplanted artery segment were adoptively transferred with human peripheral blood mononuclear cells or purified T cells from a donor allogeneic to the artery 1 week before surgery. To compare rejection of injured versus healthy tissues, these manipulations were combined. Results were analyzed ex vivo by histology, morphometry, immunohistochemistry, and mRNA quantitation or in vivo by ultrasound. Our results showed that reperfusion injury, which otherwise heals with minimal sequelae, intensifies the degree of allogeneic T cell-mediated injury to human artery segments.
  
  
  CONCLUSIONS
  We developed a new human-mouse chimeric model demonstrating interactions of reperfusion injury and alloimmunity using human cells and tissues that may be adapted to study other forms of nonimmune injury and other types of adaptive immune responses.
authors: Department of Immunobiology, Yale University School of Medicine, 10 Amistad St, New Haven, CT 06520-8089, USA.
authors: Tai
authors: T
authors: Yi
authors: Birgit
authors: B
authors: Fogal
authors: Zhengrong
authors: Z
authors: Hao
authors: Zuzana
authors: Z
authors: Tobiasova
authors: Chen
authors: C
authors: Wang
authors: Deepak A
authors: DA
authors: Rao
authors: Rafia S
authors: RS
authors: Al-Lamki
authors: Nancy C
authors: NC
authors: Kirkiles-Smith
authors: Sanjay
authors: S
authors: Kulkarni
authors: John R
authors: JR
authors: Bradley
authors: Alfred L M
authors: AL
authors: Bothwell
authors: William C
authors: WC
authors: Sessa
authors: George
authors: G
authors: Tellides
authors: Jordan S
authors: JS
authors: Pober
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D000328:Adult; D000818:Animals; D001158:Arteries / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D002678:Chimera / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology; D006085:Graft Survival / Q000276:immunology / Q000502:physiology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D015427:Reperfusion Injury / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous