In this report we examine the fate of donor cells injected via different routes. When PKH-26-labeled C57BL/6 (B6) spleen cells were intravenously (i.v.) injected into BALB/c mice, the donor cells were rejected within 3 days. In contrast, when the same B6 spleen cells were portal venously (p.v.) injected, they were trapped in the recipient liver. When allogeneic or syngeneic whole bone marrow cells (BMC) or cells in a hemopoietic stem cell (HSC)-enriched fraction were either i.v. or p.v. injected, the cells accumulated in the liver. The cells trapped in the liver were found to be wheat germ agglutinin (WGA)-positive HSC. When B6 thymocytes were p.v. or i.v. injected into BALB/c mice, they were rapidly rejected. When BALB/c mice were i.v. preimmunized with unlabeled B6 spleen cells, BMC or thymocytes, the p.v. or i.v. injected PKH-26-labeled B6 spleen cells were rejected rapidly (within 2 days). In contrast, when BALB/c mice were p.v. preimmunized with B6 spleen cells or BMC, the p.v. or i.v. injected PKH-26-labeled B6 spleen cells were not rejected. The cells responsible for the tolerance induction were found to be HSC trapped in the liver. Delayed-type hypersensitivity assays revealed that the tolerance could be maintained for more than 49 days by p.v. injection plus i.v. injection (at intervals of 2 weeks) of HSC. These findings indicate that HSC trapped in the liver play a crucial role in the induction and maintenance of p.v. tolerance.

StllTlillaryThe etiopathogenesis of focal and segmental glomerular sclerosis (FGS) remains unknown. Using a new animal model for FGS (FGS mouse), we demonstrate here that bone marrow transplantation from normal mice to FGS mice with a high grade of proteinuria (+ + +) ameliorates FGS, and that the transplantation of bone marrow cells or purified hemopoietic stem cells (HSCs) from FGS mice induces FGS in normal mice. These findings strongly suggest that FGS is a stem cell disorder; the abnormalities may be genetically programmed at the level of HSCs.

No abstract

Graft failure is a mortal complication in allogeneic bone marrow transplantation (BMT); T cells and natural killer cells are responsible for graft rejection. However, we have recently demonstrated that the recruitment of donor-derived stromal cells prevents graft failure in allogeneic BMT. This finding prompted us to examine whether a major histocompatibility complex (MHC) restriction exists between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone marrow cells (BMCs) and bones obtained from various mouse strains and analyzed the cells that accumulated in the engrafted bones. Statistically significant cell accumulation was found in the engrafted bone, which had the same H-2 phenotype as that of the BMCs, whereas only few cells were detected in the engrafted bones of the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the BMCs obtained from the MHC-compatible bone showed significant numbers of both colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings strongly suggest that an MHC restriction exists between HSCs and stromal cells.

Graft failure is a mortal complication in allogeneic bone marrow transplantation (BMT); T cells and natural killer cells are responsible for graft rejection. However, we have recently demonstrated that the recruitment of donor-derived stromal cells prevents graft failure in allogeneic BMT. This finding prompted us to examine whether a major histocompatibility complex (MHC) restriction exists between hematopoietic stem cells (HSCs) and stromal cells. We transplanted bone marrow cells (BMCs) and bones obtained from various mouse strains and analyzed the cells that accumulated in the engrafted bones. Statistically significant cell accumulation was found in the engrafted bone, which had the same H-2 phenotype as that of the BMCs, whereas only few cells were detected in the engrafted bones of the third-party H-2 phenotypes during the 4 to 6 weeks after BMT. Moreover, the BMCs obtained from the MHC-compatible bone showed significant numbers of both colony-forming units in culture (CFU-C) and spleen colony-forming units (CFU-S). These findings strongly suggest that an MHC restriction exists between HSCs and stromal cells.