The discovery of CD4+ T cell subset-defining master transcription factors and framing of the Th1/Th2 paradigm ignited the CD4+ T cell field. Advances in in vivo experimental systems, however, have revealed that more complex lineage-defining transcriptional networks direct CD4+ T cell differentiation in the lymphoid organs and tissues. This review focuses on the layers of fate decisions that inform CD4+ T cell differentiation in vivo. Cytokine production by antigen-presenting cells and other innate cells influences the CD4+ T cell effector program [e.g., T helper type 1 (Th1), Th2, Th17]. Signals downstream of the T cell receptor influence whether individual clones bearing hallmarks of this effector program become T follicular helper cells, supporting development of B cells expressing specific antibody isotypes, or T effector cells, which activate microbicidal innate cells in tissues. These bifurcated, parallel axes allow CD4+ T cells to augment their particular effector program and prevent disease.

中文翻译：

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体内 CD4+ T 细胞分化和功能：重新审视 Th1/Th2 范式。

CD4+ T 细胞亚群定义主转录因子和 Th1/Th2 范式的发现点燃了 CD4+ T 细胞领域。然而，体内实验系统的进展表明，更复杂的谱系定义转录网络指导淋巴器官和组织中的 CD4+ T 细胞分化。本综述侧重于告知体内 CD4+ T 细胞分化的命运决定层。抗原呈递细胞和其他先天细胞产生的细胞因子会影响 CD4+ T 细胞效应程序 [例如，1 型 T 辅助细胞 (Th1)、Th2、Th17]。T 细胞受体下游的信号影响具有该效应程序标志的单个克隆是否成为 T 滤泡辅助细胞，支持表达特定抗体同种型的 B 细胞或 T 效应细胞的发育，激活组织中杀菌的先天细胞。这些分叉的平行轴允许 CD4+ T 细胞增强其特定的效应程序并预防疾病。