Relationship between chimerism and tolerance in a kidney transplantation model

The persistence of donor leukocytes in recipients of organ allografts has b een associated with long-term graft acceptance, However, it remains unclear whether this peripheral donor cell microchimerism plays an active role in graft acceptance or is simply a consequence of the maintenance of sufficien t immunosuppression to avoid rejection. A model of kidney transplantation b etween swine leukocyte Ag (SLA)-matched miniature swine, in which tolerance can be established with or without immunosuppressive treatment, has been u sed to study the correlation between donor leukocyte chimerism and kidney g raft acceptance. SLA-identical kidney transplants were performed from anima ls positive for an allelic pig leukocyte Ag to animals negative for this ma rker. SLA-identical kidney transplant recipients given a 12-day course of c yclosporine (CyA) (n = 3) became tolerant, shelving stable serum creatinine levels (1-2 mg/dl) after cessation of CyA treatment. Donor cell chimerism (0.2-0.7%) was present by FAGS in all three animals with peak levels detect ed at 3 wk, Two control animals receiving SLA-identical kidney grafts witho ut CyA also showed stable serum creatinine levels and became tolerant. Howe ver, in neither of these animals could donor leukocytes be detected in the peripheral blood beyond 1 wk following transplantation. In one additional c ontrol animal, ureteral obstruction occurred at day 10, and was associated with additional peripheral chimerism, presumably related to inflammation ra ther than to immune status. These results indicate that the persistence of donor cell chimerism is not a requirement for the maintenance of tolerance to organ allografts in this model.