Molecular aspects of regulatory T cell development

Naturally arising CD4(+) regulatory T cells are critical mediators of peripheral self tolerance and immune homeostasis. Emerging evidence suggests that these cells are a dedicated T cell lineage constitutively acting in a dominant, cell extrinsic manner to regulate immune function. These observations are driving a reevaluation of our understanding of the regulation of immune homeostasis and peripheral tolerance. But despite a growing body of phenomenological data, an understanding of the molecular mechanisms underlying CD4(+) regulatory T cell development has only recently begun to emerge. This review highlights the major molecular pathways that have been implicated to date in the development of this T cell lineage.