Partial tolerance in rat renal allograft recipients following multiple blood transfusions and concomitant cyclosporine

Multiple prior administrations of donor-strain blood while under limited cyclosporine cover, consistently induce extensive rat renal allograft survival and transplantation tolerance. Yet it was hypothesized that some chronic rejection mechanisms were nevertheless operative since consistent but nonprogressive minor renal dysfunction was observed long-term. A histopathologic study on these putative tolerant rats was undertaken to test this hypothesis. Twenty long-term LEW recipients of BN renal allografts receiving the blood-CsA regimen were examined histopathologically at day 100 post-transplant. Sixteen control LEW recipients receiving only a BN renal allograft were studied acutely at day 7 posttransplant. The control recipients demonstrated a range of lesions consistent with previous studies on acute renal allograft rejection in the rat. However, tolerant recipients demonstrated mild-to-moderate lesions consistent with chronic mechanisms of rejection including the following: moderate focal interstitial mononuclear inflammatory cellular infiltration, with periglomerular and perivascular accumulation; occasional arteriolar luminal obliteration and glomerular atrophy; focal areas of moderate interstitial fibrosis; mild interstitial hemorrhage; mild-to-moderate tubular atrophy; and focal tubular necrosis. Previously our laboratory has documented that tissue-specific renal basement membrane antigens may be responsible for inciting this pattern of focal chronic interstitial inflammation. However, from the present histopathologic studies, it would appear likely that chronic rejection mechanisms in these recipients, which were defined as tolerant by immunologic criteria, involve both tissue-specific and MHC determinants. Therefore, induction of transplantation tolerance in these indefinite survivors is partial or incomplete.