Type 1 regulatory T cells: a new mechanism of peripheral immune tolerance

The lack of immune response to an antigen, a process known as immune tolerance, is essential for the preservation of immune homeostasis. To date, two mechanisms that drive immune tolerance have been described extensively: central tolerance and peripheral tolerance. Under the new nomenclature, thymus-derived regulatory T (tTreg) cells are the major mediators of central immune tolerance, whereas peripherally derived regulatory T (pTreg) cells function to regulate peripheral immune tolerance. A third type of Treg cells, termed iTreg, represents only the in vitro-induced Treg cells1. Depending on whether the cells stably express Foxp3, pTreg, and iTreg cells may be divided into two subsets: the classical CD4+Foxp3+ Treg cells and the CD4+Foxp3− type 1 regulatory T (Tr1) cells2. This review focuses on the discovery, associated biomarkers, regulatory functions, methods of induction, association with disease, and clinical trials of Tr1 cells.