Origin of Foxp3(+) cells during pregnancy.

Pregnancy establishment and maintenance represents a challenge for the maternal immune system because it has to be alert against pathogens while tolerating paternal alloantigens expressed in fetal structures. Regulatory T cells (Tregs) are important for successful implantation and involved in allotolerance towards paternal antigens. The origin and mechanisms leading to Treg generation during pregnancy at different stages remain under discussion. We report an accumulation of Helios(+) Tregs in thymus and in the lymph nodes draining the uterus at early pregnancy. At later pregnancy stages an expanded population of Foxp3(+) Tregs was generated in the periphery as we showed in a Rag-1(-/-) model of cell transfer. Our data suggest that Tregs, predominantly of thymic origin, are needed for pregnancy establishment. At later pregnancy stages an extra thymic Treg population contributes to the Treg pool in the periphery. Our data provides new insights in the origin of Tregs during pregnancy that are essential to understand natural mechanisms of tolerance acquisition.