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Regulatory T cells (Tregs) have recently taken the limelight as a therapeutic target,because they regulate virtually most adaptive immune responses.In autoimmunity,for example type 1 diabetes or multiple sclerosis,vaccines (mucosal or DNA vaccination) are able to induce Tregs that can prevent or revert the autoimmune process.Current clinical trials show encouraging results.Studies by us in animal models indicate that combination of Treg-inducing vaccines with short-course systemic immune modulators (for example anti-Cd3) can be beneficial and enhance the Treg effect and long-term tolerance.Obstacles and milestones that need to be reached to enable clinical translation will be discussed.