Mammalian Target of Rapamycin Complex 2 Controls CD8 T Cell Memory Differentiation in a Foxo1-Dependent Manner

• DOI: 10.1016/j.celrep.2015.12.095
• Publication Date: 2016-01-21T22:05:35Z
• Authors: Lianjun Zhang; Benjamin O. Tschumi; Isabel C. Lopez-M...; Susanne G. Oberle; Marten Meyer; Guerric Samson; Markus A. Rüegg; Michael N. Hall; Lluis Fajas; Dietmar Zehn; Jean-Pierre Mach; Alena Donda; Pedro Romero
• Keywords: mTORC2; FOXO1

Upon infection, antigen-specific naive CD8 T cells are activated and differentiate into short-lived effector (SLECs) memory precursor (MPECs). The underlying signaling pathways remain largely unresolved. We show that Rictor, the core component of mammalian target rapamycin complex 2 (mTORC2), regulates SLEC MPEC commitment. Rictor deficiency favors formation increases IL-2 secretion capacity without dampening functions. Moreover, mTORC2-deficient mount more potent recall responses. Enhanced in absence mTORC2 was associated with Eomes Tcf-1 upregulation, repression T-bet, enhanced mitochondrial spare respiratory capacity, fatty acid oxidation. This transcriptional metabolic reprogramming is mainly driven by nuclear stabilization Foxo1. Silencing Foxo1 reversed increased differentiation production led to an impaired response KO cells. Therefore, a critical regulator cell may be important for immunotherapy interventions.