Long-term (> 1 year) analyses of chimerism and tolerance in mixed allogeneic chimeric mice using normal mouse combinations

We examined the induction of tolerance using pancreas allografts over the l ong term (>1 year) in mice for the human application of mixed allogeneic bo ne marrow transplantation (BMT). T cell-depleted BM cells (BMCs) of C57BL/6 (B6) and C3H/He (C3H) mice were transplanted at various ratios into lethal ly irradiated B6 mice. The percentages of C3H cells in the chimeric mice gr adually decreased, finally declining to only a small percentage, except whe n the ratio of donor to recipient BMCs was 100:1. However, despite the mark ed decreases in C3H-bpe cells, all the pancreas allografts of C3H mice were accepted when more than 1% C3H cells were detected in the peripheral blood . To examine the relationships between percentages of transplanted donor ce lls and acceptance of pancreas allografts, various percentages of donor and recipient BMCs (5% to 30%) were transplanted, It was found that more than 10% donor cells were necessary for the pancreas allografts to be accepted. In vitro assays for mixed lymphocyte reaction and generation of cytotoxic T -lymphocytes revealed that spleen cells in chimeric mice accepting pancreas allografts are tolerant to both host-type and donor-type major histocompat ibility complex (MHC) determinants, but show a vigorous responsiveness to t hird-party MHC determinants. Since donor-type hemopoietic stem cells (HSCs) were detected in the BM and the liver of the chimeric mice, donor-derived HSCs and donor-derived hematolymphoid cells are responsible for the inducti on of tolerance, It should be noted that the percentage of donor-type HSCs is higher in the liver (6.2%) than in the BM (0.9%).