Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Clin Exp Immunol. 2010 Sep;161(3):490-6. doi: 10.1111/j.1365-2249.2010.04190.x.
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 (T(reg)) transplant tolerance, but the mechanism has not been clarified. To investigate whether bone marrow-derived mast cells (BMMCs) can induce T(regs) by expressing transforming growth factor beta 1 (TGF-β1) in vitro, bone marrow cells obtained from C57BL/6 (H-2(b) ) 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)(+) T(regs) in the co-cultured system were analysed by flow cytometry on day 5. The T(reg) 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.
肥大细胞(MCs)在适应性免疫反应中的作用,特别是在移植免疫反应中的作用,远未得到解决。据报道,肥大细胞是调节性 T 细胞(Treg)移植耐受的重要中介,但机制尚未阐明。为了研究骨髓来源的肥大细胞(BMMCs)是否可以通过体外表达转化生长因子β 1(TGF-β1)来诱导 Treg,从小鼠骨髓细胞中分离出 C57BL/6(H-2(b)),用白细胞介素(IL)-3(10 ng/ml)和干细胞因子(SCF)(10 ng/ml)培养 4 周。通过流式细胞术测量 BMMC 的纯度。然后将 BMMC 与 C57BL/6 T 细胞以 1:2、1:1 和 2:1 的比例进行共培养。在共培养体系中加入(实验组)或不加入(对照组)TGF-β1 中和抗体,给予抗 CD3、抗 CD28 和 IL-2。在第 5 天,通过流式细胞术分析共培养体系中 CD4+CD25+叉头框 P3(FoxP3)+Treg 的百分比。与对照组相比,所有实验组的 Treg 百分比均显著升高。这些变化是通过在共培养体系中应用 TGF-β1 中和抗体得出的。我们的结果表明,BMMC 可以通过 TGF-β1 将 CD4+T 细胞诱导为 CD4+CD25+FoxP3+T 细胞。