Regulation of T-cell responses by PTEN

The phosphoinositide 3-kinase (PI3K) signaling pathway plays a critical role in the development, activation, and homeostasis of T cells by modulating the expression of survival and mitogenic factors in response to a variety of stimuli. Ligation of the antigen receptor, costimulatory molecules, and cytokine receptors activate PI3K, resulting in the production of the lipid second messenger phosphatidylinositol-3,4,5-triphosphate (PIP(3)). A number of molecules help to regulate the activity of this pathway, including the lipid phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10). By limiting the amount of PIP(3) available within the cell, PTEN directly opposes PI3K activity and influences the selection of developing thymocytes as well as the activation requirements of mature T cells. T cells with unchecked PI3K activity, as a result of PTEN deficiency, contribute to the development of both autoimmune disease and lymphoma. This review dissects our current understanding of PI3K and PTEN and discusses why appropriate balance of these molecules is necessary to maintain normal T-cell responses.