TNIK signaling imprints CD8+ T cell memory formation early after priming

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 beta-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. Coordinate expression of multiple factors play critical roles in the regulation between effector and memory CD8(+)T cell differentiation. Here the authors show upon acute viral infection TNIK is critically required as a regulator of effector and memory T cell differentiation.