Co-stimulatory signals, cytokines and transcription factors regulate the balance between effector and memory cell differentiation during T cell activation. Here, we analyse the role of the TRAF2-/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8⁺ T cell fate during acute infection with lymphocytic choriomeningitis virus. Priming of CD8⁺ T cells induces a TNIK-dependent nuclear translocation of β-catenin with consecutive Wnt pathway activation. TNIK-deficiency during T cell activation results in enhanced differentiation towards effector cells, glycolysis and apoptosis. TNIK signaling enriches for memory precursors by favouring symmetric over asymmetric cell division. This enlarges the pool of memory CD8⁺ T cells and increases their capacity to expand after re-infection in serial re-transplantation experiments. These findings reveal that TNIK is an important regulator of effector and memory T cell differentiation and induces a population of stem cell-like memory T cells.

在T细胞活化过程中，共刺激信号，细胞因子和转录因子调节效应子和记忆细胞分化之间的平衡。在这里，我们分析TRAF2- / NCK相互作用激酶（TNIK），在肿瘤坏死因子超家族受体如CD27下游的信号分子在淋巴细胞性脉络膜脑膜炎病毒急性感染过程中对CD8 ⁺ T细胞命运的调节中的作用。启动CD8 ⁺T细胞通过连续的Wnt途径活化诱导β-catenin的TNIK依赖性核易位。T细胞活化过程中TNIK缺乏导致分化为效应细胞，糖酵解和凋亡。TNIK信号传导通过促进对称而不是不对称的细胞分裂而丰富了记忆前体。这扩大了记忆CD8 ⁺ T细胞的库，并增加了其在系列再移植实验中再次感染后的扩增能力。这些发现表明，TNIK是效应子和记忆T细胞分化的重要调节剂，并诱导了干细胞样记忆T细胞的聚集。