Regulatory T cells (Treg cells) can be divided into either thymically derived (tTreg cells) or peripherally derived (pTreg cells) populations, with the former dedicated to controlling responses to self antigens and the latter to non-self antigens. In Cell, Rudensky and colleagues examine whether pTreg cells, given their propensity for dampening responses of non-self antigens, maintain maternal-fetal tolerance. The CNS1 enhancer region is critical for pTreg cell development in that it facilitates expression of the transcription factor Foxp3. Only eutherian mammals have CNS1, suggesting that its appearance in evolution coincided with that of placentation. Indeed, in a reporter assay the equivalent enhancer regions of non-placental mammals cannot support Foxp3 expression. To directly test the role of pTreg cells in maintaining maternal-fetal tolerance, the authors use a mouse T cell receptor (TCR) transgenic system specific for paternal alloantigen and then mated with appropriate males. In the absence of maternal CNS1 there is increased embyronic resorption and signs of placental inflammation. Maintaining fetal integrity is therefore a major remit of pTreg cells.

Cell 150, 29–38 (2012)