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Long-term small bowel allograft function induced by short-term FK 506 application is associated with split tolerance
W Timmermann1, C Otto, M Gasser
1Department of Surgery, University of Wuerzburg, Germany. timmermann@chirurgie.uni-wuerzburg.de
Summary
High-dose FK 506 promotes long-term small bowel allograft survival in rats. This treatment appears to induce donor-specific tolerance, preventing chronic rejection and allowing acceptance of both small bowel and donor-specific heart grafts.
Area of Science:
- Transplantation immunology
- Graft survival research
- Immunosuppression strategies
Background:
- Chronic rejection limits long-term small bowel allograft survival.
- High-dose FK 506 can induce stable graft function post-transplantation.
Purpose of the Study:
- To investigate if long-term graft function after FK 506 treatment correlates with donor-specific tolerance.
- To analyze recipient T cell function in vivo and in vitro.
Main Methods:
- Orthotopic small bowel transplantation (SBT) in Brown Norway (BN)-to-Lewis rats.
- FK 506 administration: daily 2 mg/kg from days 0-5 (rejection model) or 0-9 (long-term model).
- Assessment of graft survival, histology, and in vitro T cell reactivity (mixed leukocyte reaction).
Main Results:
- Long-term functional model (> 250 days) showed no chronic rejection signs, unlike the rejection model (98 days mean survival).
- Donor-specific tolerance was evidenced by indefinite survival of heterotopic BN hearts (third-party DA hearts rejected within 7 days).
- In vitro, CD4+ T cells exhibited strong reactivity to both donor and third-party antigens.
Conclusions:
- High-dose FK 506 can induce split tolerance, enabling small bowel allograft acceptance without chronic rejection.
- This tolerance extends to donor-specific cardiac allografts, suggesting a broad immunomodulatory effect.
- FK 506 regimen may offer a strategy to achieve stable allograft acceptance in small bowel transplantation.