title: Human CD4+ T cells mediate rejection of porcine xenografts.
abstract: It has previously been demonstrated that xenograft rejection in rodents is dependent on CD4+ T cells. However, because of the lack of an appropriate in vivo model, little is known about the cellular basis of human T cell-mediated rejection of xenografts. In this study, we have evaluated the ability of human T cells to mediate rejection of porcine skin grafts in a novel in vivo experimental system using immunodeficient mice as recipients. Recombinase-activating gene-1-deficient mice (R-) lacking mature B and T cells were grafted with porcine skin and received human lymphocytes stimulated in vitro with irradiated porcine PBMC. Skin grafts on mice given either unseparated, activated human lymphocytes, or NK cell-depleted lymphocyte populations were rejected within 18 days after adoptive cell transfer. In contrast, skin grafts on mice given T cell-depleted human lymphocytes or saline showed no gross or histologic evidence of rejection up to 100 days after adoptive transfer. Purified CD4+ T cells were also able to mediate rejection of porcine skin grafts. These data suggest that human CD4+ T cells are sufficient to induce rejection of porcine xenografts. Thus, strategies directed toward CD4+ T cells may effectively prevent cellular rejection of porcine xenografts in humans.
authors.affiliation: Transplantation Biology Research Center, Department of Pathology, Massachusetts General Hospital, Boston, MA 02129, USA.
authors.forename: T
authors.initials: T
authors.lastname: Friedman
authors.forename: A
authors.initials: A
authors.lastname: Shimizu
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
authors.forename: J D
authors.initials: JD
authors.lastname: Seebach
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: J
authors.initials: J
authors.lastname: Iacomini
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016038:Skin Transplantation / Q000276:immunology* / Q000473:pathology; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin