Increased semi-allogeneic skin graft survival after FTY720 treatment

Abstract

FTY720 is a new compound which increases allograft survival in animal models through not fully elucidated mechanisms. Purpose: We investigated the effects of the FTY720 administration in semi-allogeneic skin graft survival in an animal model and its associated mechanisms. Methods: Both transplanted, Non-treated (Tx) and Treated (Tx+FTY720) groups were daily observed to determine the semi- allogeneic skin graft survival. In another set of experiments both groups were assessed in different time points for lymphocyte numbers and activation markers in blood and spleen. In a third experiment, mice recipients that accepted skin semi-allogeneic graft had spleen, blood, or axillary lymph node cells harvested and adoptively transferred to naïve C57BL/6 mice followed after 24 hours by a F1 skin semi- allogeneic graft transplantation. Results: Skin semi-allogeneic graft survival increased significantly in Treated Group (21.3±10.1 days) when compared to the Non-treated Group (12.9±0.4 days) (p=0.002). Five days after transplantation, Treated Group presented significantly lower amount of lymphocyte in spleen and blood (44.7±11.6x106 and 38.2±14.8%) than Non-treated mice (77.5±19.5x106 and 70.0±12.3%), respectively (p<0.005). MHC II expression in splenocytes was 26.3±5.6% in Treated, and 28.0±11.0% in Non-treated Group (p=0.3) whereas such marker presented a significant lower expression in blood: 5.6±4.1% versus 28.9±8.0% (p<0.005), respectively. Graft infiltrating cells were significantly higher in Non-treated than in Treated mice (p<0.005). Adoptive transfer caused no improvement in skin semi-allogeneic graft survival. Conclusion: The FTY720 treatment successfully improved mice skin semi-allogeneic graft survival, impairing antigen presentation and reducing graft cell infiltration. Functional tolerance after FTY720 administration was not observed.