Relationship of xenogeneic microchimerism to graft outcome in hamster-to-rat lung xenotransplantation.

BACKGROUND

In spite of the progress in allogeneic microchimerism research, few reports have dealt with the biologic relevance of xenogeneic microchimerism after organ xenotransplantation. These experiments were designed to analyze the development of xenogeneic microchimerism and its relationship to graft outcome in hamster-to-rat lung xenotransplantation.

METHODS

Golden Syrian hamsters were the donors and Lewis rats the recipients of xenogeneic lung transplantation. Animals were divided into three groups: group 1 were untreated; group 2 received cyclophosphamide (10 mg/kg/day for 6 days) and a short course of FK506 (2 mg/kg/day for 8 days); and group 3 were treated with cyclophosphamide and a long course of FK506 (2 mg/kg/day for 8 days, 1 mg/kg/day for 23 days, and then 0.5 mg/kg/day continuously). Xenogeneic microchimerisms were evaluated by use of polymerase chain reaction with primers specific for the hamster hypoxanthine phosphoribosyl-transferase gene.

RESULTS

The median graft survival times for groups 1, 2, and 3 were 3 days (n = 6), 22 days (n = 7), and 96.5 days (n = 6), respectively. In groups 1 and 2, the incidence of microchimerisms declined in parallel with the progression of rejection. In group 3, it changed dynamically, initially declining, then progressively increasing and finally disappearing.

CONCLUSIONS

In the short-term graft survivors, xenogeneic microchimerism in the peripheral blood was closely related to graft outcome. However, it showed dynamic changes and finally disappeared in long-term graft survivors, and the incidence of microchimerism at a single time point did not reflect the donor-recipient immunologic status.