Tolerance induction by allogeneic spleen cell transfusion from dexamethasone treated rats in combination with FTY720

Our previous study has demonsstrated that donor specific graft tolerance can be induced by donor spleen cells from dexamethasone (DEX ) triated rats (DEX SPC). In this study we investigated if FTY 720. a new immunosuppressant. could have a synergistic effect with DEX -SPC on the tolerance inductivity. The results showed that graft survival was further prolonged in reedients receiving both preoperative higher dose (10 mg/kg daily ) FTY 720 and DEX-SPC. However. the preoperative low dose (1 mg /kg daily ) FTY 720 did not show any syner gistic effect on tolerance induction with DEX -SPC. Unexpectedly in the perioperative regimen the lower dose FTY 720 had a synergistic effect with DEX -SPC. while the higher dose did not have. in prolonging graft survival. It is indicated that FTY 720 synergistically helps DEX-SPC to induce tolerance .The results also reinforce the viewpoint that the fortune of an allograft. tolerallced or rejected id not determjned by the nature of donor antigen, but is the function of antigen presentation and recipient T cells . Furthermore . the authors also proposed ’the way and frequency of antigen presentation model ’to interpret the apparently paradoxical results .

Adoptive transfer of FTY720-treated immature bone marrowderived dendritic cells(BMDCs) significantly reduced the spontaneous resorption rate in the CBA/J ×DBA/2 mouse model

Objective To investigate the effect of FTY720-treated immature bone marrow-derived dendritic cells（BMDCs） on the embryo resorption rate in the CBA/J× DBA/2 abortion mouse model.Methods The dendritic cells（DCs） were derived from bone marrow of DBA/2 mice, and then co-cultured with FTY720. The abortion mouse models were established by mating female CBA/J mice with DBA/2 mice. Via the CBA/J×DBA/2 abortion mouse model, six groups were established, group A： normal pregnancy model; group B： abortion mouse model with no treatment; group C： abortion mouse model injected with DC culture medium（DCCM）; group D： abortion mouse model injected with DC; group E： abortion mouse model injected with FTY720; group F： abortion model mouse injected with FTY720-DC. The differences were compared in the embryo resorption rates of the CBA/J ×DBA/2 abortion mouse model treated with FTY720-DC or different controls observed on gestation day 12 to 14, and then the microenvironment in murine pregnancy was investigated.Results The embryo resorption rate was statistically significantly decreased in group D and group E when they compared with group B and group C（P〈0.05, respectively）.Furthermore, the embryo resorption rate in group F showed a statistically significant decrease when compared with the other groups except group A（P〈0.01）. These resultssuggest that FTY720-DCs possess a notable advantage over DCs or FTY720 in reducing the embryo resorption rate of the abortion mouse model. The percentage of Th17（IL-17＋CD4＋T cells） in peripheral blood mononuclear cell（PBMC） in the abortion mouse model was 4.35%±0.34% before treated with FTY720-DC, and was1.34%±0.28% after treated with FTY720-DC（P〈0.01）. The percentage of Tregs（CD4~＋CD25~＋Foxp3~＋T cells） in PBMC was significantly increased in group F（8.35%±1.80%） as compared with group B（2.68%±0.65%）（P〈0.01）.Conclusion Adoptive transfer of FTY720-DC can statistically significantly reduce the embryo resorption rate in the CBA/J×DBA/2 abortion mouse model. The lower embryo resorption rate in the FTY720-DC treated abortion mouse model may be caused by the imbalance of Treg/Th17.