Does our current understanding of the molecular basis of immune tolerance predict new therapies for autoimmune disease?

The creation of specific immune tolerance has often been referred to as the ultimate goal of immunotherapy, because it would allow autoimmune disease to be reversed without the need for nonspecific and potentially harmful immunosuppressive therapy. Studies performed during the past decade have been immensely fruitful in terms of advances in our understanding of the cellular and molecular mechanisms of immune tolerance, and have paved the way for successful exploitation of these mechanisms for therapeutic purposes. Important developments include an increased understanding of central and peripheral tolerance, and treatment strategies that mimic the mechanisms behind deletion of self-reactive cells, the identification of crucial gene products that are involved in the induction of anergy, and the characterization of regulatory T cells and protocols for their induction and expansion for therapeutic applications. These landmarks of immune-tolerance research are summarized and their potential use in the immunotherapy of autoimmune disease discussed.