Feeding donor spleen cells both before and after transplantation significantly prolongs renal allograft survival

We have previously reported that induction of oral tolerance by feeding prior to renal transplantation results in prolonging survival of the transplant to a mean of 23 days (longest survival 37 days) compared to a mean of 8.8 days (longest survival 11 days) in unfed controls (p=0.025). In that study, Lewis rats were fed 1×10⁸ Brown Norway (BN) splenocytes daily for 5 days one week prior to transplantation. We have now examined the effect of prefeeding combined with post transplant feeding. Animals were fed as above, and in addition were fed again the day before transplantion and then once weekly post transplant. The rats were given a BN left kidney transplant and the native left kidney was removed. Three days later the native right kidney was removed, leaving the animal on only the transplanted kidney. Functional kidney survival was used as the endpoint. The animals were sacrificed when they showed gross signs of uremia. There was a pronounced improvement in survival with the combination of pre and post feeding, with three of the animals surviving 62, 82, and 105 days. Thus survival of a primary kidney allograft can be more markedly prolonged by a combination of induction of oral tolerance with donor cells pretransplantation, and maintenance of the tolerance by post transplant feeding.