Fine-tuning CD8⁺ T-cell functional responses: mTOR acts as a rheostat for regulating CD8⁺ T-cell proliferation, survival and differentiation?

Abstract

Naïve CD8⁺ T cells are instructed by antigen, co-stimulatory molecules and cytokines to undergo proliferation, clonal expansion and differentiation for effector and memory functions.  The integration of extracellular instructions induces coordinated signaling cascades and transcriptional programs to determine CD8⁺ T cell functional fate. Although, an important role for the energy sensitive kinase-mammalian target of rapamycin (mTOR) in regulating T cell proliferation and cell survival in-step with cellular metabolic status has been demonstrated, emerging information indicates that mTOR also acts as a critical regulator of effector and memory functional fates in CD8⁺ T cells. Herein, we discuss the pathways by which cellular metabolism regulates proliferation, survival and functional differentiation of CD8⁺ T cells and focus on the role of mTOR as the rheostat that strikes a balance between effector and memory differentiation of CD8⁺ T cells for enabling adaptive host immunity.