In the course of infection or autoimmunity, particular transcription factors orchestrate the differentiation of T_H1, T_H2 or T_H17 effector cells, the responses of which are limited by a distinct lineage of suppressive regulatory T cells (T_reg). T_reg cell differentiation and function are guided by the transcription factor Foxp3, and their deficiency due to mutations in Foxp3 results in aggressive fatal autoimmune disease associated with sharply augmented T_H1 and T_H2 cytokine production^,,. Recent studies suggested that Foxp3 regulates the bulk of the Foxp3-dependent transcriptional program indirectly through a set of transcriptional regulators serving as direct Foxp3 targets^,. Here we show that in mouse T_reg cells, high amounts of interferon regulatory factor-4 (IRF4), a transcription factor essential for T_H2 effector cell differentiation, is dependent on Foxp3 expression. We proposed that IRF4 expression endows T_reg cells with the ability to suppress T_H2 responses. Indeed, ablation of a conditional Irf4 allele in T_reg cells resulted in selective dysregulation of T_H2 responses, IL4-dependent immunoglobulin isotype production, and tissue lesions with pronounced plasma cell infiltration, in contrast to the mononuclear-cell-dominated pathology typical of mice lacking T_reg cells. Our results indicate that T_reg cells use components of the transcriptional machinery, promoting a particular type of effector CD4⁺ T cell differentiation, to efficiently restrain the corresponding type of the immune response.