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

BackgroundRodent models are a very helpful tool to investigate immunological mechanisms in allograft rejection. The aim of this study was to compare two different immunodeficient recipients in a humanized mouse model of arterial xenotransplantation in terms of reconstitution of the human immune system and rejection of the arterial graft.MethodsSide branches of human mammary artery were transplanted as infrarenal aortic interposition grafts into C.B-17–SCID beige and C57BL/6–Rag2−/−γc−/− recipients. 7 days after surgery mice were reconstituted with 5 × 107 human peripheral blood mononuclear cells (hu PBMCs) and 30 days after reconstitution mice were sacrificed and histologic analysis was performed. Peripheral blood and splenocytes were investigated by FACS and ELISA analysis to ensure engraftment of human CD45+ cells.ResultsTransplant arteriosclerosis developed in non-PBMC-reconstituted C.B-17–SCID beige mice (intimal proliferation: 36.31 ± 4.37%), but significantly less in C57BL/6–Rag2−/− γc−/− recipients (intimal proliferation: 12.26 ± 5.21%). After reconstitution with 5 × 107 unfractionated human PBMCs both mouse strains showed intima proliferation 30 days after reconstitution (C.B-17–SCID beige: 28.49 ± 7.95% and C57BL/6–Rag2−/− γc−/−: 44.58 ± 11.08%). Whereas only very few human CD45+ cells were found in mouse blood and spleen of C.B-17–SCID beige mice, C57BL/6–Rag2−/− γc−/− mice revealed a reliable reconstitution. In addition, levels of human IgG and IgM within the peripheral blood were markedly higher in C57BL/6–Rag2−/− γc−/− recipients.ConclusionIn this study we can show, that the use of C57BL/6–Rag2−/− γc−/− mice may be advantageous compared to C.B-17–SCID beige recipients in a humanized mouse model of vessel transplantation.