Transplantation Models in Human/Mouse Chimeras
We have developed novel transplantation models in human/mouse chimeras in order to study human immune responses to endothelial cells in vivo. The models consist of either human or pig skin or artery grafts placed in immunodeficient mice which are subsequently reconstituted with human mononuclear leukocytes. The host mice are homozygous for two genetic mutations which render them immunologically incompetent. The gene mutation for severe combined immunodeficiency (SCID) impairs the recombination of antigen receptor genes, resulting in a deficiency of functional T and B lymphocytes . The beige mutation results in an impairment of natural killer (NK) cell activity . The immunodeficient double-mutant SCID/SCID.beige/beige (SCID/beige) mice bearing human or pig grafts are immunologically reconstituted by the adoptive transfer of human peripheral blood mononuclear cells (PBMC) containing T and B lymphocytes, macrophages, and NK cells . The graft-bearing human peripheral blood leukocyte (huPBL)-SCID/beige mouse chimeras provide the milieu for the interaction of human leukocytes with human or pig endothelial cells and enable the study of human allogeneic and xenogeneic cellular immune responses in vivo.
KeywordsPeripheral Blood Mononuclear Cell Skin Graft Human Peripheral Blood Mononuclear Cell Severe Combine Immunodeficiency Transplantation Model
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- 15.Murray AG, Schechner J, Epperson DE, Sultan P, McNiff JM, Hughes CCW, Lorber MI, Askenase PW, Pober JS. Dermal microvascular injury in the Hu-PBL SCID mouse/skin allograft model is T cell-mediated and inhibited by a combination of cyclosporine and rapamycin (submitted)Google Scholar