Regulatory T cells and reproduction: how do they do it?

Regulatory T cells (Treg cells) identified by expression of Foxp3 play an important role in successful implantation and gestation. Various mechanisms have been proposed to explain their actions, and the more credible and less credible are set out in this review. Induction of Treg cells is believed to occur in response to paternal antigens in seminal plasma at the time of mating, and these Treg cells home to the uterus prior to implantation. Tolerogenic dendritic cells are proposed to play an important role in the generation of Treg cells in the draining lymph nodes and in maintaining Treg activity in the uterus. Recent data indicate that abortion in the CBAxDBA/2 model may be prevented by seminal plasma antigens from DBA/2 and BALB/c males, but H-2d restriction suggests that presentation to Treg cells might occur via a novel mechanism. The relevance of findings in mice to human pregnancy problems is also discussed.