How do regulatory T cells influence materno-fetal tolerance?

During pregnancy, the mother is host to a baby of which half the genes are from the father. This means that in effect, the baby acts like a transplanted tissue and can be rejected by the mothers immune system. The reason why this does not normally happen is not known. Our laboratory has recently shown that during pregnancy a special type of immune cell (the regulatory T cell) increases in number and we believe it may prevent rejection of the baby. This study will test the idea that these cells are important in successful pregnancy and find out what happens in women who repeatedly lose pregnancies. If successful, this work will have a major impact on how we treat women who experience recurrent abortion. It will also increase our knowledge of how the immune system functions.

Pregnancy is an immunological paradox since many antigens expressed by the fetus are derived from the father and therefore immunologically foreign. In line with other MHC mismatched transplants one might therefore expect fetal rejection, however the immune system has evolved to tolerate the fetus. We have observed that there is an increase in the number of supressive, regulatory T cells (Treg), during human pregnancy which have recently been shown to be essential for fetal tolerance. Using a combination of both human and murine systems we aim to establish the detailed kinetics of Treg changes during pregnancy and identify the mechanism underlying this. The relevance of hormonal influences on Treg behaviour will be assessed. These studies will culminate in testing the hypothesis that Treg are numerically or functionally deficient in women experiencing recurrent abortion.