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 (tT reg ) cells are the major mediators of central immune tolerance, whereas peripherally derived regulatory T (pT reg ) cells function to regulate peripheral immune tolerance. A third type of T reg cells, termed iT reg , represents only the in vitro -induced T reg cells 1 . Depending on whether the cells stably express Foxp3, pT reg , and iT reg cells may be divided into two subsets: the classical CD4 + Foxp3 + T reg cells and the CD4 + Foxp3 − type 1 regulatory T (Tr1) cells 2 . This review focuses on the discovery, associated biomarkers, regulatory functions, methods of induction, association with disease, and clinical trials of Tr1 cells.