Rag2−/− γ-chain−/− mice as hosts for human vessel transplantation and allogeneic human leukocyte reconstitution

Human Cytomegalovirus Infection Leads to Elevated Levels of Transplant Arteriosclerosis in a Humanized Mouse Aortic Xenograft Model

“…The development of transplant arteriosclerosis in cardiac allografts is a multifactorial process with macrophages, T cells, proinflammatory cytokines, adhesion molecules, growth factors and alloantibodies implicated in both initiation and progression of this chronic inflammatory process (3,19). Clinical evidence suggests that infection with HCMV may trigger the development of transplant arteriosclerosis after heart transplantation (28,29).…”

“…The success of lymphocyte-engraftment was assessed by flow cytometry 30 days after PBMC administration exactly as described previously (19). Human PBMC-engraftment was considered successful when a distinct population of human CD45 + cells was measured, representing more than 0.1% of the total circulating leukocyte population within mouse blood or more than 0.5% within mouse spleen cell samples.…”

“…Human PBMC-engraftment was considered successful when a distinct population of human CD45 + cells was measured, representing more than 0.1% of the total circulating leukocyte population within mouse blood or more than 0.5% within mouse spleen cell samples. The level of human immunoglobulin (IgM/IgG) was measured by an enzyme linked immunosorbent assay (ELISA) exactly as described in a previous study (19).…”

“…+ cells after reconstitution with human PBMCs In a previous study we have shown that Rag-2 -/-c c -/-mice showed stable engraftment after transfer of 5 × 10 7 human PBMCs (19). Therefore, on day 7 after implantation of the mammary artery graft, C57BL/6-Rag-2 -/-c c -/-recipients were reconstituted with 5 × 10 7 human PBMCs.…”

“…Lorber et al initially developed a humanized mouse model of vascular rejection by orthotopically transplanting human artery segments into immundeficient mice that were later reconstituted with human peripheral blood lymphocytes and subsequently rejected their human arterial grafts (18). We have recently shown using this experimental system, that C57BL/6-Rag-2 -/-c c -/-mice offer technical advantages over C.B-17-SCID/beige recipients as they show improved reconstitution rates with higher levels of human peripheral blood mononuclear cells (PBMCs) and more reliably reject human arterial transplants (19).…”