PDF(Pubmed)
Abstract：
T helper 1 (TH1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated TH1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the TH2 lineage: T-bet quantities were inversely correlated with the ability to express the TH2 lineage-specifying transcription factor GATA-3 and TH2 cytokines. Reprogramed TH1 cells acquired graded mixed TH1 + TH2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated TH1 cells was essential to ensure TH1 cell stability. Thus, innate cytokine signals regulate TH1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.
摘要：
T辅助1（TH1）细胞身份由谱系指定转录因子T-bet的表达定义。这里,我们基于T-bet和干扰素-γ的定量表达,利用不同体内分化TH1细胞的细胞分选,研究了T-bet表达异质性对亚群可塑性的影响.异质T-bet表达状态受病毒诱导的I型干扰素调节，即使在继发病毒感染后也能稳定维持。暴露于替代分化信号，排序后的亚群表现出分级的可塑性水平，特别是对于TH2谱系:T-bet数量与表达TH2谱系指定转录因子GATA-3和TH2细胞因子的能力呈负相关.重编程的TH1细胞获得了具有混合表观遗传景观的分级混合TH1+TH2表型。在分化的TH1细胞中持续存在T-bet对于确保TH1细胞稳定性是必要的。因此，先天细胞因子信号通过单个细胞固有变阻器调节TH1细胞可塑性,使T细胞亚群适应后续挑战.
