ENGRAFTMENT OF HUMAN KIDNEY TISSUE IN RAT RADIATION CHIMERA-I - A NEWMODEL OF HUMAN KIDNEY ALLOGRAFT-REJECTION

Background We have recently shown that lethally irradiated normal stra ins of mice and rats, reconstituted with bone marrow from severe combi ned immune deficiency (SCID) mice, can be engrafted with human periphe ral blood mononuclear cells (PBMC), Methods. The feasibility of transp lanting human renal tissue under the kidney capsule of the SCID/Lewis and SCID/nude radiation chimera and the effects of intraperitoneal inf usion of allogeneic human PBMC on the human renal implants were invest igated by histology, electron microscopy, immunohistochemistry, and fl uorescence-activated cell sorter analysis, Results. Sequential evaluat ion of the human renal implants from 10 days to 2 months after transpl antation showed that human parenchymal elements survive in the implant s up to 2 months after transplantation, The overall architecture of th e transplanted kidney tissue and the normal structure of individual ce lls in the glomeruli and tubuli were preserved. Infusion of allogeneic human PBMC after kidney implantation resulted in patchy cellular infi ltrates, composed mainly of activated human T cells, and Led to prompt rejection of the human renal tissue, whereas no signs of inflammation were observed;in human renal implants of chimeric rats that did not r eceive human PBMC, Treatment with OKT3 antibody, anti-human CD25 antib ody, or CTLA4Ig fusion protein in vivo ameliorated the rejection proce ss. Conclusions. Human adult kidney fragments transplanted into SCID-l ike rats transiently retain competent parenchymal structures. When the se grafts are combined with allogeneic human PBMC, acute cellular reje ction develops, We suggest that this chimeric model might be useful fo r the investigation of the effects of experimental manipulation on the kinetics of the inflammatory response during human renal allograft re jection.