Regulatory T cells in autoimmune disease

In recent years, the understanding of regulatory T cell (Treg cell) biology has expanded considerably. Key observations have challenged the traditional definition of Treg cells and have provided insight into the underlying mechanisms responsible for the development of autoimmune diseases, with new therapeutic strategies that improve disease outcome. This Review summarizes the newer concepts of Treg cell instability, Treg cell plasticity and tissue-specific Treg cells, and their relationship to autoimmunity. Those three main concepts have changed the understanding of Treg cell biology: how they interact with other immune and non-immune cells; their functions in specific tissues; and the implications of this for the pathogenesis of autoimmune diseases. Treg cells have a critical role in maintaining peripheral tolerance. In this Focus Review, Dominguez-Villar and Hafler describe how the instability and plasticity of Treg cells can contribute to the breakdown of tolerance and lead to autoimmune disease.