THYMUS-MEDIATED IMMUNE TOLERANCE TO RENAL-ALLOGRAFT IS DONOR BUT NOT TISSUE SPECIFIC

Studies were conducted in Lewis (RT1I) rats to determine whether the process of unresponsiveness to kidney graft induced by the intrathymic glomerular transplantation were donor-strain specific as suggested by previous studies (Remuzzi et al., Lancet 1991;337:750-752). When glomeruli from Sprague-Dawley rats were injected in the thymus of Lewis rats, the subsequent kidney graft from a "third party" Brown-Norway (RT1n) rejected within 9 to 14 days. Moreover, an alternative site for glomerular antigen inoculation, such as i.p. administration, failed to induce a state of unresponsiveness to renal allograft. Whether tolerance was tissue specific was investigated by intrathymic injection of a preparation of donor blood cells that only included white cells. Such a maneuver, followed 10 days later by a kidney transplant, allowed indefinite renal graft survival in all animals, whereas all rats injected intrathymically with blood cell medium alone rejected the kidney graft in 8 to 11 days. Shortening the time interval between intrathymic injection of blood cells and kidney transplantation still allowed the graft to survive indefinitely. Finally, Lewis (RT1I) rats with chronic renal failure injected intrathymically with blood cells from Brown-Norway (RT1n) rats tolerated indefinitely a subsequent kidney graft from the same donor. These findings indicate that (1) the induction of immune tolerance to renal allograft induced by intrathymic injection of antigens is donor but not tissue specific; (2) the time interval between intrathymic injection of donor cells and the subsequent kidney transplantation can be reduced to 24 h; and (3) uremia does not preclude the possibility of renal allograft tolerance after the thymus procedure.