The phosphatase PTEN-mediated control of PI-3 kinase in T(regs) cells maintains homeostasis and lineage stability

Foxp3(+) regulatory T cells (T(regs)) are required for immune homeostasis. One notable distinction between conventional T cells (T(conv)) and T(regs) is differential phosphatidylinositol 3-kinase (PI3K) activity: only T(conv) downregulate PTEN, the primary negative regulator of PI3K, upon activation. Here, we show that control of PI3K in T(regs) is essential for lineage homeostasis and stability. Mice lacking Pten in T(regs) developed an autoimmune-lymphoproliferative disease characterized by excessive T(H)1 responses and B cell activation. Diminished control of PI3K activity in T(regs) led to reduced CD25 expression, accumulation of Foxp3(+)CD25(−) cells and ultimately, loss of Foxp3 expression in these cells. Collectively, these data demonstrate that control of PI3K signaling by PTEN in T(regs) is critical to maintain their homeostasis, function and stability.