Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-10-7
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1535-3702
pubmed:author
pubmed:issnType
Print
pubmed:volume
228
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1096-104
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:14530522-Animals, pubmed-meshheading:14530522-Antigens, CD3, pubmed-meshheading:14530522-Antigens, CD4, pubmed-meshheading:14530522-Antigens, CD45, pubmed-meshheading:14530522-Antigens, CD8, pubmed-meshheading:14530522-Female, pubmed-meshheading:14530522-Flow Cytometry, pubmed-meshheading:14530522-Graft Rejection, pubmed-meshheading:14530522-Graft vs Host Disease, pubmed-meshheading:14530522-Humans, pubmed-meshheading:14530522-Immunohistochemistry, pubmed-meshheading:14530522-Leukocytes, Mononuclear, pubmed-meshheading:14530522-Lymphocytes, pubmed-meshheading:14530522-Male, pubmed-meshheading:14530522-Mice, pubmed-meshheading:14530522-Mice, Inbred NOD, pubmed-meshheading:14530522-Mice, SCID, pubmed-meshheading:14530522-Receptors, Interleukin-2, pubmed-meshheading:14530522-Skin Transplantation, pubmed-meshheading:14530522-Spleen, pubmed-meshheading:14530522-beta 2-Microglobulin
pubmed:year
2003
pubmed:articleTitle
Alloimmune injury and rejection of human skin grafts on human peripheral blood lymphocyte-reconstituted non-obese diabetic severe combined immunodeficient beta2-microglobulin-null mice.
pubmed:affiliation
University of Massachusetts Medical School, Worcester, Massachussetts 01605, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't