Impact of Immunosuppressive Drugs on the Metabolism of T Cells

Int Rev Cell Mol Biol. 2018:341:169-200. doi: 10.1016/bs.ircmb.2018.05.009. Epub 2018 Jun 19.


Energetic metabolism supports rapid cell growth and proliferation, differentiation, polarization, and effector functions of T cells. T lymphocytes have the remarkable plasticity that allows them to shape their metabolism to adapt to extracellular and intracellular cues, a process that involves molecular modules referred to as "metabolic checkpoints" that sense metabolic signals and transduce effector messages. These metabolic checkpoints may represent a novel therapeutic strategy for immune modulation. Chemical immunosuppressive drugs including mammalian target of rapamycin inhibitors (sirolimus and everolimus), calcineurin inhibitors (tacrolimus and cyclosporine), and purine and pyrimidine synthesis inhibitors (6-mercaptopurine, mycophenolic acid, and methotrexate) are widely prescribed for the treatment of autoimmune and inflammatory diseases and for controlling alloimmunity in interfering with the signals that activate and allow T cells to proliferate. Emerging evidence indicates that these drugs also target T-cell metabolism and metabolic checkpoints, which, as a consequence, could contribute to their immunosuppressive effects. These examples raise the issue of how the modulation of these metabolic checkpoints can regulate T-cell activation, differentiation, and function. In this review we highlight emerging concepts about the modulation of metabolic reprogramming in T-cell responses by immunosuppressive drugs and how potential therapeutic interventions influence T-cell fate and effector function.

Keywords: Glucose; Immunometabolism; Immunosuppression; Immunosuppressive drugs; Metabolic checkpoint; Metabolism; Mitochondria; T lymphocytes.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*


  • Immunosuppressive Agents