EFFECT OF DONOR-SPECIFIC SPLENOCYTES VIA PORTAL-VEIN AND FK506 IN RATSMALL-BOWEL TRANSPLANTATION

Background. To investigate the role of the liver in immune responses a fter small bowel transplantation, donor-specific splenocytes were infu sed perioperatively, via the portal vein, in a rat heterotopic small b owel transplant model(1, 2, 3). Methods, Heterotopic small bowel trans plantation between the fully allogenic Brown Norway (BN) (RT1(n)) and Lewis (RT1(1))strain rats were performed, We prepared donor splenocyte s from BN or third-party WKA (RT1(k)) rat spleens for Lewis hosts and injected the splenocytes perioperatively via the host portal vein or t he systemic vein, The hosts were treated with a short course of the im munosuppressive agent, FK506 (0.5 mg/kg, 0-3 days postoperatively), fo llowing the experimental protocols. Results, Untreated Lewis hosts rej ected BN small bowel grafts at 5.4 +/- 0.9 days (n = 8), BN splenocyte s given alone caused fatal graft-versus-host disease in six of eight a nimals, and two others died from graft rejection, FK506 alone did not significantly prolong graft survival (6.3 +/- 1.0 days, n = 10), Howev er, BN splenocytes injected via the portal vein, combined with FK506, prolonged graft survival to 12.7 +/- 2.1 days (n = 12, P < 0.01) and 1 0 of 12 rats survived more than 70 days, This was donor antigen specif ic, BN splenocytes administered systemically caused fatal graft-versus -host disease in all recipients, and FK506 did not ameliorate this, Hi stologic findings of graft rejection were remarkably mild in the recip ients of the combined therapy, compared with the recipients that were given FK506 alone, Down-regulation of one-way mixed lymphocyte reactio n to BN splenocytes was observed in the splenocytes of the tolerant ho sts, Conclusions, Combined administration of donor splenocytes and FK5 06 reduced allograft rejection and prolonged survival in this rat mode l of small bowel transplantation.