23 research outputs found
Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion
The effect of deoxyspergualin (DSG) on rejection and graft-versus-host disease (GVHD) after small bowel transplantation
Involvement of endothelin in graft-versus-host disease after rat small bowel transplantation
Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation
Effect of small bowel transplantation, denervation and ischaemia on rat intestinal microflora
Effect of anti-CD4 monoclonal antibody administration on rat small bowel allograft survival and circulating leukocyte populations
Small-bowel transplantation in the rat with a nonsuture cuff technique: Technical and immunological considerations
Relevance of tumor necrosis factor to graft-versus-host disease after small bowel transplantation
Inhibition of donor-derived T cells trafficking into target organs by FTY720 during acute graft-versus-host disease in small bowel transplantation
In small bowel transplantation (SBTx), graft-versus-host disease (GVHD) is mediated by donor-derived T cells recognizing host major histocompatibility complex (MHC) alloantigens, and represents an important immunological event influencing life in experimental and clinical situations. We evaluated the possibility that a new sphingosine 1-phosphate receptor agonist, FTY720, could diminish GVHD in a rat SBTx model through traffic alteration of donor-derived T cells in target organs. Heterotopic SBTx was performed using a parent (WF)-into-F(1) (WF × ACI) rat combination. Recipient survival, body weight, histopathology, donor-derived T cell subpopulation and cytokine production were compared with untreated controls. FTY720 inhibited lethality and histopathological changes in target organs when administered at 0·5 mg/kg, possibly due to sequestration of donor-derived T cells in the intestinal graft. FTY720 caused a significant reduction in donor T cell numbers in target organs by promoting these cells to home into donor, but not recipient, secondary lymphoid tissues. FTY720 significantly decreased production of interferon (IFN)-γ in target organs. These findings indicate that FTY720 effectively reduced recirculation of activated donor-derived T cells and recruitment to target organs in GVHD, and was also associated with down-regulated IFN-γ production. These properties may offer the potential to treat ongoing GVHD in SBTx