Characterization of tolerance mechanisms at the fetal-maternal interface - Treg cells and novel tolerance-related molecules

During pregnancy, the maternal immune system has to tolerate the persistence of paternal alloantigens without affecting anti-infectious immune responsiveness. Tolerance towards the semiallogenic fetus involves a number of mechanisms associated with modifications of the immune status of the mother. These cellular and molecular mechanisms are still poorly understood. Treg cells seem to have an important role during normal human and murine pregnancy. Moreover, Treg transferred to an abortion-prone female could rescue from abortion. Previous data suggest that Treg may be effective in avoiding fetal allo-rejection by interacting with tissues and creating a tolerant privileged microenvironment characterized by high expression of HO-1, TGF-b and LIF. To better understand this phenomenon we aim to identify novel tolerance molecules associated with this Treg-protective effect locally. To understand the origin of these cells, a further objective of this work will be to clarify the Treg origin and migration routes during pregnancy. These data will allow to better understand natural tolerance mechanisms and may be very helpful in designing therapeutic approaches tending to avoid immunological pregnancy loss.