FOXO3 and lymphopenia: Increased PI3K signaling has been shown to suppress Treg cell differentiation and function,14, 17, 28 in part through inhibitory effects on Foxo1 and Foxo3a.19, 21, 22 Therefore we investigated the frequency of FOXP3+ Treg cells, as well as FOXP3 expression levels, in patients with defects in PTEN. Although absolute Treg cell numbers are lower in patients with PHTS, because of the CD4 lymphopenia, similar frequencies of Treg cells were found in peripheral blood, as well as in MALT, in patients with PHTS compared with control subjects (Fig 2, A and B).