TRANSPLANTATION TOLERANCE IN PRIMATES FOLLOWING TOTAL LYMPHOID IRRADIATION AND ALLOGENEIC BONE MARROW INJECTION II. RENAL ALLOGRAFTS

Abstract

A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation. In the preceding paper we described the production of transplantation tolerance for orthotopic liver allografts in the chacma baboon after several regimens of total lymphoid irradiation (TLI) and allogeneic BM injection (1). A program of fractionated irradiation of the entire torso in one field (8 × 200 rad) gave the most consistent results, but a single dose of 300 rad to the torso also prolonged liver allograft survival significantly. An important observation was that organ grafting could be delayed 3 to 4 weeks after completing TLI and BM injection. BM chimerism in low degree was observed in only two of the four baboons receiving fractionated TLI. It was also pointed out that the per kilogram body weight doses of nulceated BM cells injected were approximately one-twentieth of those found to be necessary in rodent models (2), and that results might be improved by increasing these doses. One animal has survived for more than 6 months, despite deferring challenge with liver transplantation and donor BM injection for 2½ months after receiving two fractions (total 800 rad) of TLI. In the studies reported here, we have used kidney allografts to test further this concept in the baboon. We have increased the BM dosages, and have evaluated the effect in this model of delaying both BM injection and kidney transplantation after completing TLI.