Abstract
In our previous work we demonstrated that the use of donor specific bone marrow infusions ( DSBMI ) after small bowel transplantation did not improve the graft survival after a short course of immunossupression. PURPOSE: In the current study, we evaluated whether recipient preconditioning with different regimens of radiation combined with DSBMI may enhance small bowel allograft survival with minimum recipient morbidity. METHODS: Heterotopic small bowel transplantation (SBTx) was performed with Lewis rats as recipients and DA rats as donors, which were immunossupressed with a short course of tacrolimus (FK 506 ) at 1mg/Kg/day for 5 days and distributed in 4 groups: group 1 (n= 4) without both irradiation and DSBMI; Groups 2 (n= 6), 3 (n= 9) and 4 (n= 6) received 100 x 10(6) DSBM cells at the time of the transplant. Groups 3 and 4 were irradiated with 250 and 400 rd respectively. Animals were examined daily for clinical signs of rejection or GVHD. Blood samples were taken weekly for chimeric studies by FC and intestinal biopsies were performed every 2 weeks. RESULTS: Animals in G1 and G2 had minimal rejection at day 15 after SBTx while GVHD was clinically and histologically characterized in G 3 and G 4. Total chimerism and T-cell chimerism was higher in irradiated groups when compared to non-irradiated groups. With exception of G1 and 2 where rejection was the cause of death, all animals in G3 and 4 died of GVHD. CONCLUSION:We concluded that low cytoreductive of irradiation can successfully decrease the graft rejection but not prevent the occurrence of GVHD.
Highlights
Despite the improvements in post-transplant immunosupressive regimens, the control of allograft rejection is still dependent on the use of nonspecific immunosupressive agents, which is frequently associate to complications, such as infections and lymphoproliferative disorders (1).The successfully induction of specific tolerance continues to be a challenger in recipients after a solid organ transplantation
An increased susceptibility to severe rejection and increased mortality were observed in groups treated with donor specific bone marrow infusions (DSBMI) when started early after transplant and immunosupressed with a short course of tacrolimus
graft-versus-host disease (GVHD) was clinically and histologically characterized as moderate to severe only in groups submitted to irradiation
Summary
The successfully induction of specific tolerance continues to be a challenger in recipients after a solid organ transplantation. Methods to enhance the natural microchimerism are currently explored using donor specific bone marrow (BM) cells, in order to facilitate the development of donor-specific tolerance after transplant. In a previous work (2) we compared the effect of single or multiple donor specific bone marrow infusions (DSBMI) after small bowel transplantation. An increased susceptibility to severe rejection and increased mortality were observed in groups treated with DSBMI when started early after transplant and immunosupressed with a short course of tacrolimus. Severe rejection were observed in recipients after delayed infusions that were given upon discontinuation of immunosupression, suggesting that immunosuppressive and/or immunomodulatory strategies may be needed for longer periods of time when BM are used
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