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-reconstitu ted severe combined immunodeficiency (SCID) (hu-PBL-SCID) mice as a mo del for human islet allograft rejection. The function of xenografted h u-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 st udy porcine islet rejection in humans. Chimeric mice were used as the recipients of porcine islets to reveal the mechanisms of xenograft rej ection in humans. SCID mice were reconstituted with 30 x 10(6) of hu-P BL initially, and 10 x 10(6) of antihuman CD3-primed PBL was injected intraperitoneally 2 days later as a booster. An additional booster inj ection provided greater possibility (86.7%, n = 15) of chimera establi shment 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 FAGS staini ng. In an in vivo study, immunofluorescent analysis of a frozen sectio n 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 mi ce provide a useful model for investigating the real-life situation of porcine islet xenograft rejection in humans.