Regulatory T cells in pregnancy.

Tolerance mechanisms are responsible for the survival of the fetus within the maternal uterus without being attacked by the cells of the maternal immune system despite their direct contact. Regulatory T cells (Treg) were claimed to be important players in the tolerance towards the fetus bearing alloantigens. Recent evidence confirmed an augmentation in the number of Treg during pregnancy and, most importantly, diminished numbers of Treg were associated with immunological rejection of the fetus. This could be prevented by adoptively transferring CD4(+)/CD25(+) Treg cells from normal pregnant mice into abortion-prone animals. Treg prevented abortion while creating a transient tolerant microenvironment characterized by high levels of TGF-beta, LIF, and HO-1. Downregulated levels of Treg were accordingly also reported during human miscarriage. Furthermore, we have evidence suggesting that, to be protective, Treg need to be activated by male antigens during pregnancy.