Immune tolerance induced by donor antigen and cyclophosphamide in rat fetal small bowel transplantation.
OBJECTIVE
Donor specific immune tolerance is thought to be the ideal state for the recipient after organ transplantation. The administration of donor antigens and cyclophosphamide has been reported to induce donor specific immune tolerance in heart or liver transplantation. However, the effectiveness of this method for small bowel transplantation has not yet been studied. We assessed the cyclophosphamide induced immune tolerance on rat fetal small bowel transplantation.


METHODS
Lewis rats (RT1(1), n=99) were used as recipients while either F344 (RT1(1), n=44) or WKAM (RT1(u), n=47) rats were used as donors. The combination of F344 and Lewis rats produces an immunologically low responder, while that of WKAM and Lewis rat produces a high responder. Bone marrow and spleen cells were harvested from the donor rats and 3x10(8)/kg of each were administrated to the recipient rats intravenously on day 0. Next, cyclophosphamide was given either divisionally or bolously. The fetal small bowel of the same strain as the donor was transplanted into the rectus muscle of the recipient abdominal wall on day 10. On day 17, all grafts were taken out and graft survival was thereafter evaluated. The body weight of recipient was also assessed.


RESULTS
Most of the grafts (87.5%) survived in the F344-Lewis rat (low responder) combination using the divisional administration of 120 mg/kg of cyclophosphamide. Histologically, most of them showed the whole layers of the intestinal architectureto be well preserved. The weight loss of the recipient was minimal after divisional administration. In contrast, no graft survived in the WKAM-Lewis rat (high responder) combination.


CONCLUSIONS
Immune tolerance is considered to be induced by the administration of donor specific antigen and cyclophosphamide in an immunologically low responder combination. Therefore, this method is expected to be useful as an adjuvant therapy and may also be able to reduce the dose of immunosuppressive agents in living-related clinical small intestinal transplantation.
Nakao
Makoto
M
Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Taguchi
Tomoaki
T
Ogita
Keiko
K
Nishimoto
Yuko
Y
Suita
Sachiyo
S
D000818:Animals; D000941:Antigens / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D005333:Fetus; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007421:Intestine, Small / Q000637:transplantation*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014019:Tissue Donors
D000941:Antigens; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide