Control of T cell tolerance by phosphatase and tensin homolog

The in vivo maintenance of immune tolerance is critically dependent on regulatory T (T reg ) cells, a lineage of CD4 + T cells expressing the transcription factor Foxp3 that exerts immunoregulatory function. Because of the potential benefit of using T reg cells for cellular immunotherapy in clinical settings, including autoimmune disease and transplantation, much attention has been directed at understanding the signals that govern T reg cell development, function, and homeostasis. Studies with genetically modified mouse models have shown that the lipid phosphatase PTEN (phosphatase and tensin homolog), the predominant negative regulator of the PI3K/Akt pathway in T cells, has multiple functions in sustaining T cell–mediated immune tolerance in vivo . In addition to its role in maintaining T cell homeostasis, the PI3K/Akt pathway also has an essential role in T cell development and lineage commitment, contributing to the cell fate decision between conventional and regulatory T cells.