The Mammalian Target of Rapamycin: Linking T Cell Differentiation, Function, and Metabolism

In the two-signal model of T cell activation, the outcome of antigen recognition is determined by the integration of multiple cues in the immune microenvironment. mTOR is an evolutionarily conserved PI3-kinase family member that plays a central role in integrating environmental cues in the form of amino acids, energy, and growth factors. Recently, an increasingly important role for mTOR in directing T cell activation and differentiation has become apparent. Here we review recent findings demonstrating the ability of mTOR to interpret signals in the immune microenvironment and program the generation of CD4⁺ effector versus regulatory T cells, the generation of CD8⁺ effector versus memory cells, T cell trafficking, and T cell activation versus anergy. The key theme to emerge from these studies is that the central role of mTOR provides a direct link between T cell metabolism and function.