Adaptation and Modulation of Memory and Regulatory T Cells in Pregnancy

Abstract

During pregnancy immune adaptations induce tolerance of the fetal cells which are partly derived from the father, while normally the immune system would reject foreign cells. Adaptations of the maternal immune response are necessary for pregnancy success since insufficient immune adaption is associated with pregnancy pathologies such as infertility, recurrent pregnancy loss, fetal growth restriction, spontaneous preterm birth, and preeclampsia. In this thesis several studies are presented in which memory T cells and regulatory T cells were investigated in healthy pregnancies, pregnancies complicated by preeclampsia, and pregnancies in which medication was administered. In the first part of this thesis, we investigated multiple immune cell populations during and after healthy human pregnancies. We found that pregnancy has a persistent effect on memory T cells. Besides, we found that these cells had different characteristics in women pregnant for the first time compared to women who were pregnant before. These findings support the hypothesis that memory T cells might contribute to a lower risk of pregnancy complications in a following pregnancy. The second part of this thesis describes the studies which showed that memory T cell populations and regulatory T cell populations are present in different proportions during and after pregnancies complicated by preeclampsia compared to women during and after healthy pregnancies. This suggests that these cells might play a role in the pathophysiology of preeclampsia. Part 3 presents a study on the effects of prednisolone treatment in early pregnancy on regulatory T cells in a mouse model. There is debate on the use of prednisolone in fertility treatments. Here, we showed that prednisolone exposure in early pregnancy disrupts the regulatory T cell response later in pregnancy. This might have consequences since we know that regulatory T cells are important for healthy pregnancy. Moreover, prednisolone treatment in early pregnancy appeared to affect the development of offspring until adulthood. This project therefore questions its safety of use. Altogether, this thesis further elucidated the adaptations of memory- and regulatory T cell populations in healthy pregnancies and preeclampsia. The data presented suggest a possible beneficial role for these T cells in human reproduction which needs further functional studies to be defined. In addition, the results emphasize the necessity for more studies to investigate the safety of immune modulatory drug use in pregnancy.