Upon infection with an intracellular pathogen, cytotoxic CD8⁺ T cells develop diverse differentiation states characterized by function, localization, longevity, and the capacity for self-renewal. The program of differentiation is determined, in part, by FOXO1, a transcription factor known to integrate extrinsic input in order to specify survival, DNA repair, self-renewal, and proliferation. At issue is whether the state of T cell differentiation is specified by initial conditions of activation or is actively maintained. To study the spectrum of T cell differentiation, we have analyzed an infection with mouse cytomegalovirus, a persistent-latent virus that elicits different cytotoxic T cell responses characterized as acute resolving or inflationary. Our results show that FOXO1 is continuously required for all the phenotypic characteristics of memory-effector T cells such that with acute inactivation of the gene encoding FOXO1, T cells revert to a short-lived effector phenotype, exhibit reduced viability, and manifest characteristics of anergy.

感染细胞内病原体后，细胞毒性 CD8 ⁺ T 细胞会形成多种分化状态，其特征是功能、定位、寿命和自我更新能力。分化程序部分由 FOXO1 决定，FOXO1 是一种转录因子，已知可整合外源输入以指定生存、DNA 修复、自我更新和增殖。问题在于 T 细胞的分化状态是由初始激活条件决定的还是主动维持的。为了研究 T 细胞分化谱，我们分析了小鼠巨细胞病毒的感染，这是一种持续潜伏的病毒，可引发不同的细胞毒性 T 细胞反应，其特征为急性消退或膨胀。我们的结果表明，记忆效应 T 细胞的所有表型特征持续需要 FOXO1，因此，随着编码 FOXO1 的基因急性失活，T 细胞恢复为短命效应表型，表现出活力降低，并表现出无反应性特征。