Directing T cell differentiation and function with small molecule inhibitors

Regulatory T (Treg) cells that express the signature transcription factor Foxp3 safeguard against autoimmunity and immune pathology. Recent studies show that a signaling network with the components phosphatidyl inositol 3 kinase (PI3K), Akt, and the mammalian target of rapamycin (mTOR) regulates the de novo expression of Foxp3 in CD4 T cells. In addition to CD4 T cell differentiation, PI3K/Akt/mTOR signaling also controls T cell migration. Here we review the new data, consider their evolutionary context and discuss their potential implications for immunotherapy.