During pregnancy a unique situation arises in which the mother's immune system accepts the fetus, which carries both maternal and paternal genes, and does not reject it as can occur in solid organ... Show moreDuring pregnancy a unique situation arises in which the mother's immune system accepts the fetus, which carries both maternal and paternal genes, and does not reject it as can occur in solid organ transplantation. The aim of this dissertation was to unravel the immunological mechanisms that ensure tolerance during a healthy pregnancy and uncover how alterations could contribute to the development of pregnancy complications, such as pre-eclampsia and preterm birth.We applied the new technique mass cytometry and the associated computational analyzes to map all immune cells of the mother during a healthy pregnancy. Furthermore, we demonstrated the presence of three types of functional regulatory CD4+ T cells, identified a phenotype of CD8+ T cells that can offer both tolerance and immunity against infections, and demonstrated potential cross-reactivity of T cells against fetal allo-antigens. The results described in this thesis have contributed to a better understanding of healthy pregnancies and form a basis on which further research can be built. Show less
Human pregnancy is an interesting immunological paradox. The fetus is a semi-allograft, carrying paternal and maternal genes but is not rejected by the maternal immune system. The placenta is a key... Show moreHuman pregnancy is an interesting immunological paradox. The fetus is a semi-allograft, carrying paternal and maternal genes but is not rejected by the maternal immune system. The placenta is a key player in maintaining the pregnancy, since this fetus-derived organ is in direct contact with the mother. This thesis describes the results of investigations on the immune regulation at the fetal-maternal interface with emphasis on two immunological challenges during pregnancy. First, preeclampsia, which might be immunologically related to host versus graft disease as seen in solid organ transplantation and second, egg donation (ED) pregnancies, which show that even complete allogeneic fetal allografts can be tolerated by the mother. The immunological mechanisms involved in acceptance of the totally allogeneic fetus in ED pregnancies are not well understood yet. It is possible that it leads to differential immunological regulation. This hypothesis is tested in this thesis. We found differential immunological interactions in successful ED and in preeclamptic pregnancies compared with naturally conceived pregnancies. These results indicate that preeclampsia and ED pregnancies are indeed immunological challenges during pregnancy. It is a scientific challenge to further reveal the immunological mechanisms, contributing to precious information for the fields of immunology, transplantation and obstetrics. Show less
