Lu et al. have suggested that recipient-derived MCs are crucial for Treg-mediated peripheral tolerance [11], indicating that the function of mast cells in suppressing immune responses was related to Tregs. Our study showed that CD4+CD25+ FoxP3+ cells could be induced by BMMCs. This finding may supply a new mechanism suggesting that MCs are crucial for Treg-mediated transplant tolerance [11]. This method may also become a new method for the induction of Tregsin vitro. Our results showed that the highest percentage of Tregs was found in the highest ratio (2:1) of BMMCs to T cells. TGF-β1 expression in BMMCs was determined in our experimental

groups. Jahanyar et al. concluded that mast cell-derived TGF-β may serve as important mediators for Treg activation in allografts [21], and other studies reported that the percentage of Tregs increased with the higher level of added TGF-β1 [22]. Therefore, it seems that the increase of Tregs with a higher ratio of BMMCs HM781-36B price may be related to more BMMCs-derived TGF-β1. Consistent with previous studies, and in order to test whether BMMC-derived TGF-β1 is involved in Carfilzomib chemical structure the generation of Tregs, TGF-β1

neutralizing antibody was added to the co-culture system [4]. The conversion of Tregs was reduced significantly by the TGF-β1 neutralizing antibody, but the TGF-β1 neutralizing antibody could not reverse Treg induction completely. The percentages of Tregs were still higher than control, even with the application of TGF-β1 neutralizing antibody. Whether there were some other mediators derived from BMMCs which also had the potential to induce Tregs is debatable. Metz considered that IL-4 may be related to the suppression function of MC in the immune response [6]. Therefore, IL-4 neutralizing antibody was applied to block the function of IL-4, but there were no significant differences after the application of IL-4 neutralizing antibody.

Although this study did not provide direct evidence for BMMCs as the main source of TGF-β1, it suggests that BMMC-derived TGF-β1 is involved in the regulation of Treg cell generation in vitro. Our experiment concerned mainly the relationship between mast cells and Tregsin vitro. Huang et al. showed that tumour-infiltrating mast cells may promote tumour growth through one way of increasing Treg cells in vivo[23]. Demeclocycline This leads us to conclude that perhaps Tregs can be induced by mast cells in vivo. More studies will be conducted to clarify this phenomenon. In conclusion, our experiments demonstrate that Tregs can be induced by BMMCs in vitro, and secreting TGF-β1 by BMMCs is one of the principal factors for the effect. This finding may provide new evidence that mast cells have the ability to suppress immune responses by way of Treg induction. Furthermore, the study may supply new data for identifying clearly the role of mast cells in immune systems. This work was funded by National Natural Science Foundation of China (no.