Foxp3 and natural regulatory T cells: key to a cell lineage?

The recent characterization of a mutant strain of mice generated five decades ago in a program to study ionizing radiation in mammals (and, ironically, derived from a nonmutagenized control animal) is helping to dissect a now resurgent area of immunology. Despite a vast literature during the 1970s, the study of suppressor T cells had been largely abandoned until the publication of several seminal papers rekindled interest in what are today generally referred to as regulatory T (TR) cells. The identification of the transcription factor Foxp3 as the gene responsible for the defect in scurfy mice, and subsequently, the demonstration of its critical involvement in the generation of TR cells, provides an important molecular insight into this essential cell lineage.