Fate of allogeneic or syngeneic cells in intravenous or portal vein injection: Possible explanation for the mechanism of tolerance induction by portal vein injection

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.