Control of T cell tolerance by phosphatase and tensin homolog.

The in vivo maintenance of immune tolerance is critically dependent on regulatory T (Treg ) cells, a lineage of CD4(+) T cells expressing the transcription factor Foxp3 that exerts immunoregulatory function. Because of the potential benefit of using Treg cells for cellular immunotherapy in clinical settings, including autoimmune disease and transplantation, much attention has been directed at understanding the signals that govern Treg 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.