IMMUNOBIOLOGY Brief report Wild-type FOXP3 is selectively active in CD4CD25hi regulatory T cells of

Forkhead box P3 (FOXP3) is constitu-tively expressed by CD4CD25hi regula-tory T cells (nTregs). Mutations of FOXP3 cause a severe autoimmune syndrome known as immune dysregulation poly-endocrinopathy enteropathy X-linked, in which nTregs are absent or dysfunc-tional. Whether FOXP3 is essential for both differentiation and function of hu-man nTreg cells remains to be demon-strated. Because FOXP3 is an X-linked gene subject to X-chromosome inactiva-tion (XCI), we studied 9 healthy female carriers of FOXP3 mutations to investi-gate the role of wild-type (WT) versus mutated FOXP3 in different cell subsets. Analysis of active WT versus mutated (mut)–FOXP3 allele distribution revealed a random pattern of XCI in peripheral blood lymphocytes and in naive and memory CD4T cells, whereas nTregs ex-pressed only the active WT-FOXP3. These data demonstrate that expression of WT-FOXP3 is indispensable for the presence of a normal nTreg compartment and sug-gest that FOXP3 is not necessary for effector T-cell differentiation in humans. (Blood. 2009;114:4138-4141