Cellular and molecular determinants for the development of natural and induced regulatory T cells

Regulation of immune responses to self and foreign antigens is critically dependent on suppressive CD4⁺ T cells characterized by expression of Foxp3. The large majority of regulatory T (Treg) cells develop in the thymus as a stable suppressive lineage. However, under the proper physiological conditions, conventional peripheral CD4⁺ T lymphocytes also develop into Treg cells, particularly in the gut mucosa and inflammatory tissue sites. This review will focus on our current understanding of the immunological and molecular signals controlling the development of thymic derived natural (n)Treg and peripheral converted induced (i)Treg cells. Given the importance of Foxp3 in the development of these cells, particular attention is placed on how such signals are integrated to induce and maintain the expression of this signature transcriptional regulator of Treg cells.