Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Cell Mol Immunol. 2019 Jul;16(7):634-643. doi: 10.1038/s41423-019-0220-6. Epub 2019 Mar 12.
CD4 T helper cells are key regulators of host health and disease. In the original model, specialized subsets of T helper cells are generated following activation through lineage-specifying cytokines and transcriptional programs, but recent studies have revealed increasing complexities for CD4 T-cell differentiation. Here, we first discuss CD4 T-cell differentiation from a historical perspective by highlighting the major studies that defined the distinct subsets of T helper cells. We next describe the mechanisms underlying CD4 T-cell differentiation, including cytokine-induced signaling and transcriptional networks. We then review current and emerging topics of differentiation, including the plasticity and heterogeneity of T cells, the tissue-specific effects, and the influence of cellular metabolism on cell fate decisions. Importantly, recent advances in cutting-edge approaches, especially systems biology tools, have contributed to new concepts and mechanisms underlying T-cell differentiation and will likely continue to advance this important research area of adaptive immunity.
CD4+ T 辅助细胞是宿主健康和疾病的关键调节者。在最初的模型中，T 辅助细胞的特化亚群是在通过谱系特异性细胞因子和转录程序激活后产生的，但最近的研究揭示了 CD4+T 细胞分化的日益复杂性。在这里，我们首先通过强调定义 T 辅助细胞不同亚群的主要研究，从历史角度讨论 CD4+T 细胞的分化。接下来，我们描述 CD4+T 细胞分化的机制，包括细胞因子诱导的信号转导和转录网络。然后，我们回顾分化的当前和新兴主题，包括 T 细胞的可塑性和异质性、组织特异性效应以及细胞代谢对细胞命运决定的影响。重要的是，前沿方法（尤其是系统生物学工具）的最新进展为 T 细胞分化的新概念和新机制做出了贡献，并可能继续推动适应性免疫这一重要研究领域的发展。
