Immunologic benefits of longer graft in rat allogenic small bowel transplantation.
BACKGROUND
The effect of graft length on rejection reaction in small bowel transplantation (SBT), which is poorly understood, is tested using rat allogenic SBT models with a short course of tacrolimus.


METHODS
Inbred Brown Norway rats (major histocompatibility complex: RT1) and Lewis rats (RT1) were used as donors and recipients, respectively. The intestinal tract of the recipient was partially or totally replaced by segmental (15 cm) or whole (70 cm) donor intestine, using two different SBT models. With tacrolimus treatment (0.64 mg/kg per day, 0-13 postoperative days, intramuscularly), recipients' body weights and their survival were evaluated. To compare the extent of peripheral chimerism, donor passenger leukocytes were followed using flow cytometry with a donor-specific monoclonal antibody, OX-27. For the periodical histologic analysis, heterotopic SBT and protocol biopsies of the graft were also performed with short or long intestinal grafts.


RESULTS
In a classical Monchik and Russell orthotopic SBT model, whole SBT recipients survived more than 60 days. However, all of the allogenic segmental SBT recipients died within 14 days without histologic sign of graft rejection. In the modified orthotopic SBT model using a cuff technique without systemic clamping, all recipients with segmental allograft survived longer than 29 days. However, recipients with whole graft tended to survive longer than those with segmental graft. The suffering period, lasting from the onset of rejection to death, was significantly shorter in the segmental group than in the whole group. Flow cytometric analysis showed that recipients with whole intestinal grafts had significantly higher ratio of donor passenger leukocytes in peripheral blood. Histologic studies of the protocol biopsies showed that the shorter graft tended to be more severely rejected than the longer graft.


CONCLUSIONS
We have demonstrated experimentally that long intestinal grafts have immunologic advantage over short grafts.
Fujishiro
Jun
J
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, 329-0498, Japan.
Tahara
Kazunori
K
Inoue
Seiichiro
S
Kaneko
Takashi
T
Kaneko
Michio
M
Hashizume
Kohei
K
Kobayashi
Eiji
E
D000818:Animals; D006085:Graft Survival / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007421:Intestine, Small / Q000276:immunology / Q000637:transplantation*; D008285:Major Histocompatibility Complex; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000627:therapeutic use; D016042:Transplantation, Heterotopic / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology*
D007166:Immunosuppressive Agents; D016559:Tacrolimus