The immune compartment at the maternal-fetal interface throughout human pregnancy

Zwan, A. van der (2020)

Doctoral Thesis

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 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.

• Pregnancy
• Immunology
• Placenta
• Trophoblasts
• Decidua
• Tolerance
• T cell exhaustion
• Regulatory T cells
• Heterologous immunity
• HLA-C

• All authors: Zwan, A. van der
• Supervisor: Claas, F.H.J.
• Co-supervisor: Heidt, S.; Tilburgs, T.
• Committee: Borts, J.; Kooten, C. van; Moffett, A.; Saito, S.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2020-02-06
• ISBN (print): 9789463326032