Transforming growth factor beta 1 plays an important role in inducing CD4+CD25+forhead box P3+ regulatory T cells by mast cells

Abstract

Summary The role of mast cells (MCs) in the generation of adaptive immune responses especially in the transplant immune responses is far from being resolved. It is reported that mast cells are essential intermediaries in regulatory T cell (Treg) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce Tregs by expressing transforming growth factor beta 1 (TGF-β1) in vitro, bone marrow cells obtained from C57BL/6 (H-2b) mice were cultured with interleukin (IL)-3 (10 ng/ml) and stem cell factor (SCF) (10 ng/ml) for 4 weeks. The purity of BMMCs was measured by flow cytometry. The BMMCs were then co-cultured with C57BL/6 T cells at ratios of 1:2, 1:1 and 2:1. Anti-CD3, anti-CD28 and IL-2 were administered into the co-culture system with (experiment groups) or without (control groups) TGF-β1 neutralizing antibody. The percentages of CD4+CD25+forkhead box P3 (FoxP3)+ Tregs in the co-cultured system were analysed by flow cytometry on day 5. The Treg percentages were significantly higher in all the experiment groups compared to the control groups. These changes were deduced by applying TGF-β1 neutralizing antibody into the co-culture system. Our results indicated that the CD4+ T cells can be induced into CD4+CD25+FoxP3+ T cells by BMMCs via TGF-β1.