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Alloimmune injury and rejection of human skin grafts on human peripheral blood lymphocyte-reconstituted non-obese diabetic severe combined immunodeficient beta2-microglobulin-null mice.
Turgeon, Nicole A; Banuelos, Scott J; Shultz, Leonard D; Lyons, Bonnie L; Iwakoshi, Neal; Greiner, Dale L; Mordes, John P; Rossini, Aldo A; Appel, Michael C.
Afiliação
  • Turgeon NA; University of Massachusetts Medical School, Worcester, Massachussetts 01605, USA.
Exp Biol Med (Maywood) ; 228(9): 1096-104, 2003 Oct.
Article em En | MEDLINE | ID: mdl-14530522
Small animal models with the capacity to support engraftment of a functional human immune system are needed to facilitate studies of human alloimmunity. In the present investigation, non-obese diabetic (NOD) severe combined immunodeficient (scid) beta2-microglobulin-null (B2mnull) mice engrafted with human peripheral blood lymphocytes (hu-PBL-NOD-scid B2mnull mice) were used as in vivo models for studying human skin allograft rejection. Hu-PBL-NOD-scid B2mnull mice were established by injection of human spleen cells or PBLs and transplanted with full-thickness allogeneic human skin. Human cell engraftment was enhanced by injection of anti-mouse CD122 antibody. The respective contributions of human CD4+ and CD8+ cells in allograft rejection were determined using depleting antibodies. Human skin grafts on unmanipulated NOD-scid B2mnull mice uniformly survived but on chimeric hu-PBL-NOD-scid B2mnull mice exhibited severe immune-mediated injury that often progressed to complete rejection. The alloaggressive hu-PBLs did not require prior in vitro sensitization to elicit targeted effector cell activity. Extensive mononuclear cell infiltration directed towards human-origin endothelium was associated with thrombosis and fibrin necrosis. No evidence of graft-versus-host disease was detected. Either CD4+ or CD8+ T cells may mediate injury and alloimmune rejection of human skin grafts on hu-PBL-NOD-scid B2mnull mice. It is proposed that Hu-PBL-NOD-scid B2mnull mice engrafted with human skin will provide a useful model for analysis of interventions designed to modulate human allograft rejection.
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Base de dados: MEDLINE Assunto principal: Linfócitos / Transplante de Pele / Doença Enxerto-Hospedeiro Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2003 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Linfócitos / Transplante de Pele / Doença Enxerto-Hospedeiro Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2003 Tipo de documento: Article