Orthotopic liver/small bowel transplantation in rats: a microsurgical model inducing tolerance.
Liver cirrhosis in patients with short bowel syndrome is successfully treated in humans by simultaneous liver/small bowel transplantation. However, until now, a clinically relevant experimental rat model for this procedure has not existed. We therefore established a protocol that, for the first time in rats, allows the simultaneous transplantation of arterialized liver and small bowel into an orthotopic position. Short-term immunosuppression induced not only allograft acceptance but tolerance (as demonstrated by indicator heart/skin transplantation). The immunosuppressive dose required to achieve this result was dramatically less than that of protocols for successful small bowel transplantation alone. Immunohistochemistry detected a transient rejection crisis before tolerance. During this crisis, apoptotic recipient-type T lymphocytes, mainly CD8+ cells, accumulated in the liver but not in the small bowel allograft. The initiation of T-cell apoptosis is one possible explanation for the specific immunosuppressive effect of the liver allograft, which also supports the simultaneously transplanted small bowel allograft in our model.
Meyer
D
D
Department of Surgery, University of Würzburg, Josef-Schneider Strasse 2, D-97080 Würzburg, Germany.
Thorwarth
W M
WM
Otto
C
C
Gassel
H J
HJ
Timmermann
W
W
Ulrichs
K
K
Thiede
A
A
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008866:Microsurgery; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016559:Tacrolimus