Graduate Institute of Clinical Medicine, National Taiwan University, Taipei City, 10048, Taiwan R.O.C.
Department of Medical Research, National Taiwan University Hospital, Taipei City, 10002, Taiwan R.O.C.
Sci Rep. 2017 Apr 12;7:46348. doi: 10.1038/srep46348.
The role of B cells in the development of CD4 regulatory T cells has been emphasized recently. Our previous studies have demonstrated that the antigen-presenting splenic B cells converted naïve CD4CD25 T cells into CD4CD25Foxp3 T cells without additional cytokines or chemicals with regulatory activity and that referred to as Treg-of-B cells. The present study further showed that Treg-of-B cells increased the IL-10-producing population, and the expression of c-Maf, inducible T-cell co-stimulator (ICOS) as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA4) after repeated stimulation of B cells in a cell-cell contact-dependent manner. Long-term cultured Treg-of-B cells exerted IL-10 and CTLA4-mediated antigen-specific suppressive activity; moreover, the single antigen-specific Treg-of-B cells inhibited in a non-antigen-specific fashion. In conclusion, these results suggest that repeated stimulation of B cells induced IL-10-producing CD4Foxp3 regulatory T cells in a contact-dependent manner and these Treg-of-B cells possess IL-10 and CTLA4-dependent suppressive function.
B 细胞在 CD4 调节性 T 细胞（Treg）的发育中的作用最近受到了重视。我们之前的研究表明，抗原呈递的脾 B 细胞在没有额外的具有调节活性的细胞因子或化学物质的情况下，将初始 CD4+CD25-T 细胞转化为 CD4+CD25+Foxp3+Treg，我们称之为 B 细胞来源的 Treg（Treg-of-B）。本研究进一步表明，Treg-of-B 细胞通过细胞间接触依赖性方式，在反复刺激 B 细胞后增加了 IL-10 产生细胞群的数量，以及 c-Maf、诱导性 T 细胞共刺激分子（ICOS）和细胞毒性 T 淋巴细胞相关蛋白 4（CTLA4）的表达。长期培养的 Treg-of-B 细胞发挥了 IL-10 和 CTLA4 介导的抗原特异性抑制活性；此外，单一抗原特异性 Treg-of-B 细胞以非抗原特异性方式抑制。总之，这些结果表明，B 细胞的反复刺激以接触依赖性方式诱导了产生 IL-10 的 CD4+Foxp3+调节性 T 细胞，并且这些 Treg-of-B 细胞具有 IL-10 和 CTLA4 依赖性抑制功能。
