title: Human cell-mediated rejection of porcine xenografts in an immunodeficient mouse model.
abstract: BACKGROUND
  In this study, we describe the development of a novel experimental system in which rejection of porcine skin grafts by human peripheral blood cells can be studied directly in vivo in immunodeficient mice.
  
  
  METHODS
  To construct a small animal model of discordant xenograft rejection, recombinase-activating gene-deficient mice (R-) lacking both mature B and T cells were grafted with porcine skin grafts and administered, by adoptive cell transfer, human cells stimulated in vitro with irradiated porcine peripheral blood cells to create Hu-R- mice.
  
  
  RESULTS
  R- mice accepted porcine skin grafts indefinitely without the need for immunosuppression. In contrast, Hu-R- mice were able to reject porcine skin grafts. Immunohistochemical analysis of rejecting skin grafts revealed the accumulation of human T cells around dermal porcine vessels and focally in the epidermis. Graft rejection was manifested by vascular endothelial cell proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage. The tissue damage observed in the rejecting grafts was similar to that observed in delayed primate anti-porcine cell-mediated rejection of vascularized organ xenografts.
  
  
  CONCLUSIONS
  The development and characterization of a small animal model, to study cellular immune responses of human cells to discordant xenografts in vivo, should provide a convenient means for asking mechanistic questions related to discordant xenotransplantation, and may also provide a practical system for testing new approaches designed to prevent xenograft rejection.
authors.affiliation: Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: P A
authors.initials: PA
authors.lastname: DellaPelle
authors.forename: J D
authors.initials: JD
authors.lastname: Seebach
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: J
authors.initials: J
authors.lastname: Iacomini
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000473:pathology; D016038:Skin Transplantation / Q000276:immunology*; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*