Human peripheral blood lymphocyte-reconstituted, severe combined immunodeficient mice as a model for porcine islet xenograft rejection in humans.
Previously we established human peripheral blood lymphocyte-reconstituted severe combined immunodeficiency (SCID) (hu-PBL-SCID) mice as a model for human islet allograft rejection. The function of xenografted hu-PBL was confirmed to reject human alloislets in hu-PBL-SCID mice. In this study, we modified this model as a porcine islet xenograft to study porcine islet rejection in humans. Chimeric mice were used as the recipients of porcine islets to reveal the mechanisms of xenograft rejection in humans. SCID mice were reconstituted with 30 x 10(6) of hu-PBL initially, and 10 x 10(6) of antihuman CD3-primed PBL was injected intraperitoneally 2 days later as a booster. An additional booster injection provided greater possibility (86.7%, n = 15) of chimera establishment as well as a higher human immunoglobulin concentration in SCID mice than the single injection group. In an in vitro assay, sera from hu-PBL-SCID mice were found to recognize porcine islets by FACS staining. In an in vivo study, immunofluorescent analysis of a frozen section showed that human immunoglobulins adhered to the xenografted porcine islet under the kidney capsule of hu-PBL-SCID mice. Although no mouse immunoglobulins were detected on sections, mouse complement (C3) was shown to adhere to the xenografted porcine islet. Thus, hu-PBL-SCID mice provide a useful model for investigating the real-life situation of porcine islet xenograft rejection in humans.
Shiroki
R
R
Department of Urology, Fujita Health University School of Medicine, Aichi, Japan.
Nazirrudin
B
B
Hoshinaga
K
K
Naide
Y
Y
Scharp
D W
DW
Mohanakumar
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D017690:Cell Transplantation; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007075:Immunoglobulin M / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D007668:Kidney / Q000378:metabolism; D051379:Mice; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D003176:Complement C3; D007075:Immunoglobulin M; D016650:Fluorescein-5-isothiocyanate