Effect of donor-specific splenocytes via portal vein and FK506 in rat small bowel transplantation.
BACKGROUND
To investigate the role of the liver in immune responses after small bowel transplantation, donor-specific splenocytes were infused perioperatively, via the portal vein, in a rat heterotopic small bowel transplant model.


METHODS
Heterotopic small bowel transplantation between the fully allogenic Brown Norway (BN) (RT1n) and Lewis (RT1[1]) strain rats were performed. We prepared donor splenocytes from BN or third-party WKA (RT1k) rat spleens for Lewis hosts and injected the splenocytes perioperatively via the host portal vein or the systemic vein. The hosts were treated with a short course of the immunosuppressive agent, FK506 (0.5 mg/kg, 0-3 days postoperatively), following the experimental protocols.


RESULTS
Untreated Lewis hosts rejected BN small bowel grafts at 5.4+/-0.9 days (n=8). BN splenocytes given alone caused fatal graft-versus-host disease in six of eight animals, and two others died from graft rejection. FK506 alone did not significantly prolong graft survival (6.3+/-1.0 days, n=10). However, 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 10 of 12 rats survived more than 70 days. This was donor antigen specific. BN splenocytes administered systemically caused fatal graft-versus-host disease in all recipients, and FK506 did not ameliorate this. Histologic findings of graft rejection were remarkably mild in the recipients of the combined therapy, compared with the recipients that were given FK506 alone. Down-regulation of one-way mixed lymphocyte reaction to BN splenocytes was observed in the splenocytes of the tolerant hosts.


CONCLUSIONS
Combined administration of donor splenocytes and FK506 reduced allograft rejection and prolonged survival in this rat model of small bowel transplantation.
Miyauchi
T
T
First Department of Surgery, University of Tokushima, School of Medicine, Tokushima City, Japan.
Ishikawa
M
M
Tashiro
S
S
Hisaeda
H
H
Nagasawa
H
H
Himeno
K
K
D000818:Animals; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000637:transplantation*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D019990:Perioperative Care; D011169:Portal Vein; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000637:transplantation*; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016559:Tacrolimus