THE KIDNEY TRIGGERS GRAFT-VERSUS-HOST DISEASE IN EXPERIMENTAL COMBINED TRANSPLANTATION OF KIDNEY AND STEM CELL-ENRICHED PERIPHERAL LEUKOCYTES

As a preclinical step to human studies with combined stem cell-enriche d peripheral leukocytes and organ transplantation from the same donor, a series of studies in rats was undertaken. These studies indicated t hat Lewis rats infused intravenously with major histocompatibility com plex-incompatible (from Brown-Norway rats), stem cell-enriched periphe ral leukocyte preparation alone never developed graft-versus-host dise ase (GHVD), However, GVHD invariably manifested in all animals a few d ays after the kidney was transplanted in rats that had been previously primed with stem cell-enriched peripheral leukocytes from the same ki dney donor strain. GVHD was prevented by substituting the crude prepar ation of stem cell-enriched peripheral leukocytes with a purified prep aration that was almost completely free of T lymphocytes. However, in these latter experiments all rats rejected their kidney graft within 1 0 days from the surgery, In rats previously given the crude stem cell- enriched peripheral leukocyte preparation, perioperative administratio n of the fusion protein CTLA4Ig also prevented GVHD and prolonged kidn ey graft survival up to 106 to 175 days. By contrast, animals with kid ney transplants, which were given CTLA4Ig without stem cells, rejected their grafts within 35 days, All together, these findings may possibl y contribute to the creation of rationally designed strategies of comb ining organ and bone marrow from the same donor to enhance mixed chime rism and prolong survival after organ transplantation.