Characterization of the immune landscape at the maternal-fetal interface and the role of endogenous T cells in the pathogenesis of preeclampsia.

Background

Preeclampsia (PE) is a major cause of maternal and fetal mortality and morbidity worldwide. The roles and characteristics of immune cells in PE pathogenesis remain incompletely understood.

Methods

We collected the basal decidua, placentas, fetal membranes and umbilical cord blood from PE patients and healthy pregnant women as well as the placentas, uteri, livers, spleens and peripheral blood from normal pregnant and N-nitro-L-arginine methyl ester (L-NAME) induced PE mice, and performed multicolor flow cytometry to characterize the immune-cell landscapes. In addition, endogenous CD4+ or CD8+ T cells were depleted in the PE mice by intraperitoneal injection of anti-CD4 (GK1.5) or anti-CD8 (2.43) depletion monoclonal antibody, and then PE-related symptoms were evaluated.

Results

Immune cells showed distinct enrichment patterns across different tissues at the maternal-fetal interface in pregnant women, and the immune landscape at the maternal-fetal interface differed between PE patients and healthy pregnancies. Similar results were observed in the normal pregnant and L-NAME induced PE mice. Furthermore, in vivo depletion of CD4+ T cells, but not CD8+ T cells, could ameliorate PE-related symptoms by attenuating the elevated blood pressure, reducing the urine protein-to-creatinine ratio, and alleviating the placental impairment and maternal inflammatory responses in the PE mice.

Conclusion

Our study demonstrated a distinct landscape of immune cells at the maternal-fetal interface in normal and PE pregnancies and revealed a pathogenetic role of endogenous CD4+ T cells in PE development, which provided new insights into PE pathogenesis and potential targets for PE prevention.