Inhibition of donor‐derived T cells trafficking into target organs by FTY720 during acute graft‐ versus ‐host disease in small bowel transplantation

Summary 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.