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Foxp3⁺CD4⁺CD25⁺ regulatory T (T_reg) cells are essential for the prevention of autoimmunity^,. T_reg cells have an attenuated cytokine response to T-cell receptor stimulation, and can suppress the proliferation and effector function of neighbouring T cells^,. The forkhead transcription factor Foxp3 (forkhead box P3) is selectively expressed in T_reg cells, is required for T_reg development and function, and is sufficient to induce a T_reg phenotype in conventional CD4⁺CD25^- T cells^,,,. Mutations in Foxp3 cause severe, multi-organ autoimmunity in both human and mouse^,,. FOXP3 can cooperate in a DNA-binding complex with NFAT (nuclear factor of activated T cells) to regulate the transcription of several known target genes. However, the global set of genes regulated directly by Foxp3 is not known and consequently, how this transcription factor controls the gene expression programme for T_reg function is not understood …