Ex vivo perfusion of canine pancreaticoduodenal allografts using class-II-specific monoclonal antibody delays the onset of acute rejection

Abstract

In the following study, we investigated whether ex vivo perfusion of canine pancreaticoduodenal allografts prior to transplantation using a class-II-specific monoclonal antibody (MoAb) OKia1) could prevent acute rejection. Untreated grafts were rejected within 6 days after transplantation, and all of these recipients suffered severe hyperglycemia. In contrast, in recipients who received grafts which underwent ex vivo class-II-specific MoAb perfusion treatment, the mean urinary amylase levels were sustained significantly higher (11 733 ± 4493 vs. 3274 ± 2108 U/L on day 7, P < 0.005), and mean fasting blood glucose (FBG) levels remained within the normal range (13.4 ± 5.8 vs. 23.4 ± 3.9 mM on day 7, P < 0.0005).Low doses of cyclosporin A (CsA) were necessary in order to maintain lower FBG levels. Histopathology analysis on day 7 after transplantation showed that endotheliitis and necrosis were much less prominent in the MoAbtreated grafts. In the light of our results, we conclude that ex vivo perfusion of canine pancreaticoduodenal allografts using a class-11-specific MoAb is effective in delaying the onset of acute rejection, and low doses of CsA could extend this effect.In pancreas transplantation, the most powerful stimulus for the initiation of acute rejection has been shown to come from interstitial dendritic cells (DCs ), expressing large quantities of major histocompatibility complex (MHC) class II antigens. DCs are known to be present in the exocrine pancreas and circulate rapidly through the Offprint requests to: K. Miyoshi, First