ENGRAFTMENT OF HUMAN KIDNEY TISSUE IN RAT RADIATION CHIMERA-II - HUMAN FETAL KIDNEYS DISPLAY REDUCED IMMUNOGENICITY TO ADOPTIVELY TRANSFERRED HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS AND EXHIBIT RAPID GROWTH AND DEVELOPMENT

Background. Transplantation of human kidney tissue under the kidney ca psule of immunodeficient animals (severe combined immunodeficiency [SC ID]I Lewis and SCID/nude chimeric rats). and the subsequent intraperit oneal infusion of allogeneic human peripheral blood mononuclear cells (PBMC), results in a rapid and consistent human renal allograft reject ion. We investigated the consequences of grafting human fetal kidney f ragments instead of the adult tissue. Methods. The development of huma n fetal kidney tissue and its interaction with allogeneic human PBMC i n chimeric rats were analyzed by histology, immunohistochemistry, and in situ hybridization. Results. We report successful establishment of human fetal kidney to SCID/Lewis and SCID/nude chimeric rats. The intr arenal human fetal renal implants displayed rapid growth and maintaine d numerous developing glomeruli and tubular structures up to 4 months after transplantation. In contrast to the adult human kidney, infusion of allogeneic human PBMC resulted in either minimal human T-cell infi ltration or abundant nonrejecting T-cell infiltrates, characterized by a reduced number of T cells of the CD45RO(+) or HLA-DR+ subsets, both leading to less tissue destruction as well as to continued growth of the human fetal renal tissue. This observation was found to be related to the reduced protein expression of tissue HLA class I and PI, inter cellular adhesion molecule 1, and vascular adhesion molecule 1 in the fetal grafts compared with the adult grafts. Lack of tissue expression of Fas Ligand in the fetal grafts suggests that the latter does not c ontribute to the delayed rejection of human fetal kidneys. Conclusions . Our model should be useful for the study of human fetal renal develo pment and the human alloresponse against fetal tissue.