Regulation of T cells by mTOR: the known knowns and the known unknowns

• mTOR has emerged as a critical integrator of cues from the immune microenvironment.
• By coordinating immunologic and metabolic programs, mTOR guides T cell fate decisions.
• Mechanisms by which mTOR activity impacts T cell differentiation are not fully defined.
• Contradictory findings highlight areas requiring further investigation.

Mammalian/mechanistic target of rapamycin (mTOR) is emerging as an important integrator of environmental cues critical for the regulation of T cell activation, differentiation, and function. Recent studies leveraging pharmacologic inhibition or T cell specific genetic deletion of signaling components in the mTOR pathway have provided important insights into the mechanisms involved, and have been informative in defining targets downstream of mTOR that promote immune regulation. However, these studies have also presented confusing and, at times, contradictory findings, highlighting the complexities involved in examining the mTOR pathway in distinct contexts. Here, we review current understanding of the roles of mTOR in T cell biology, highlighting emerging concepts and areas of investigation where the precise role of mTOR has yet to be fully discerned.