Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Sanquin Landsteiner Laboratory for Blood Cell Research, Amsterdam, The Netherlands.
Adv Immunol. 2018;137:43-82. doi: 10.1016/bs.ai.2017.12.003. Epub 2018 Feb 1.
CD8 T cells clear primary infections with intracellular pathogens and provide long-term immunity against reinfection. Two different types of CD8 T cells are responsible for these functions: short-lived effector T cells and memory T cells. The cellular relationship between these two types of CD8 T cells has been subject to much investigation. Both cell types can derive from a single naïve CD8 T cell precursor. Their generation requires a fate choice early during a T cell response. As a result, two populations of T cells emerge. One of these consists of terminally differentiated short-lived effector T cells. The other contains cells able to develop into long-lived memory T cells. A foundation for development of these two populations may be laid during the first division of an activated naïve T cell precursor, as a consequence of asymmetric segregation of fate-determining factors into the daughter cells. Nonetheless, the binary choice between the two lineages is strongly influenced by signals, which ensure that the differentiation process is matched with the needs posed by the infection. Here, we will discuss the genetic and metabolic programs governing differentiation of these two lineages as well as the processes leading to their induction and consolidation to create bistability. These processes involve extensive lateral inhibition between the programs as well as positive feedback between the genetic programs and the signaling pathways responsible for their induction. These features will be highlighted by discussing the role of the Notch signaling pathway in guiding the decision between the two lineages.
CD8 T 细胞清除细胞内病原体的初次感染，并提供针对再次感染的长期免疫力。两种不同类型的 CD8 T 细胞负责这些功能：短期存活效应 T 细胞和记忆 T 细胞。这两种类型的 CD8 T 细胞之间的细胞关系一直是研究的热点。这两种细胞类型都可以来源于单个幼稚 CD8 T 细胞前体。它们的产生需要在 T 细胞反应早期进行命运选择。因此，两种 T 细胞群体出现。其中一种由终末分化的短期存活效应 T 细胞组成。另一种包含能够发育成长期记忆 T 细胞的细胞。这些两个群体的发育基础可能是在激活的幼稚 T 细胞前体的第一次分裂期间形成的，这是由于命运决定因素在子细胞中的不对称分配。尽管如此，两种谱系之间的二进制选择受到信号的强烈影响，这些信号确保分化过程与感染所带来的需求相匹配。在这里，我们将讨论控制这两种谱系分化的遗传和代谢程序，以及导致它们诱导和巩固以产生双稳定性的过程。这些过程涉及到程序之间的广泛的侧向抑制，以及遗传程序和负责诱导它们的信号通路之间的正反馈。通过讨论 Notch 信号通路在指导两种谱系之间的决策中的作用，将突出这些特征。
