T follicular helper (T FH ) cells are essential for effective antibody responses, but deciphering the intrinsic wiring of mouse T FH cells has long been hampered by the lack of a reliable protocol for their generation in vitro. We report that transforming growth factor–β (TGF-β) induces robust expression of T FH hallmark molecules CXCR5 and Bcl6 in activated mouse CD4 + T cells in vitro. TGF-β–induced mouse CXCR5 + T FH cells are phenotypically, transcriptionally, and functionally similar to in vivo–generated T FH cells and provide critical help to B cells. The study further reveals that TGF-β–induced CXCR5 expression is independent of Bcl6 but requires the transcription factor c-Maf. Classical TGF-β–containing T helper 17 (T H 17)–inducing conditions also yield separate CXCR5 + and IL-17A–producing cells, highlighting shared and distinct cell fate trajectories of T FH and T H 17 cells. We demonstrate that excess IL-2 in high-density T cell cultures interferes with the TGF-β–induced T FH cell program, that T FH and T H 17 cells share a common developmental stage, and that c-Maf acts as a switch factor for T FH versus T H 17 cell fates in TGF-β–rich environments in vitro and in vivo.

中文翻译：

---

TGF-β 通过 c-Maf 指定小鼠 CD4 + T 细胞中 T FH 与 TH 17 细胞的命运

T 滤泡辅助器 (T跳频）细胞对于有效的抗体反应至关重要，但破译小鼠 T 细胞的内在接线跳频细胞的体外生成长期以来一直受到缺乏可靠方案的阻碍。我们报告转化生长因子-β (TGF-β) 诱导 T 的强烈表达跳频激活小鼠 CD4 中的标志分子 CXCR5 和 Bcl6+体外 T 细胞。TGF-β诱导的小鼠CXCR5+时间跳频细胞在表型、转录和功能上与体内产生的 T 细胞相似跳频细胞并为 B 细胞提供重要帮助。该研究进一步揭示，TGF-β诱导的CXCR5表达不依赖于Bcl6，但需要转录因子c-Maf。含有经典 TGF-β 的 T 辅助细胞 17 (TH17)–诱导条件也产生单独的CXCR5+和 IL-17A 产生细胞，强调了 T 细胞共有和不同的细胞命运轨迹跳频和TH17 个细胞。我们证明高密度 T 细胞培养物中过量的 IL-2 会干扰 TGF-β 诱导的 T跳频细胞程序，T跳频和TH17 个细胞具有共同的发育阶段，c-Maf 充当 T 的开关因子跳频与 TH17 细胞在富含 TGF-β 的体外和体内环境中的命运。