Decreased Expression of Cytotoxic Proteins in Decidual CD8(+) T Cells in Preeclampsia

SIMPLE SUMMARY: CD8(+) T cells are prominent decidual cells in the third trimester of healthy human pregnancy. They have a cytotoxic capacity which may control invasion of extravillous trophoblast and therefore affect placentation and play the role in development of preeclampsia. In this study, we examined the expression of CD8(+) T cells in decidual tissue and peripheral blood of women with severe and mild preeclampsia in comparison to gestational age-matched healthy pregnancies. Additionally, the expression of cytotoxic proteins in CD8(+) T cells was examined in order to specify their subpopulations. ABSTRACT: In our study, we aimed to establish expression of cytotoxic CD8(+) T cells in the decidua basalis and the maternal peripheral blood (mPBL) of severe and mild preeclampsia (PE) and compare to healthy pregnancies. Decidual tissue and mPBL of 10 women with mild PE, 10 women with severe PE, and 20 age-matched healthy pregnancy controls were analyzed by double immunofluorescence and qPCR, respectively. By double immunofluorescence staining, we found a decreased total number of cells/mm(2) in decidua basalis of granulysin (GNLY)(+) (p ˂ 0.0001), granzyme B (GzB)(+)(p ˂ 0.0001), GzB(+)CD8(+)(p ˂ 0.0001), perforin (PRF1)(+) (p ˂ 0.0001), and PRF1(+)CD8(+) (p ˂ 0.01) in the severe PE compared to control group. Additionally, we noticed the trend of lower mRNA expression for GNLY, granzyme A (GZMA), GzB, and PRF1 in CD8(+) T cells of mPBL in mild and severe PE, with the latter marker statistically decreased in severe PE (p ˂ 0.001). Forkhead box P3 (FOXP3) mRNA in CD8(+) T cells mPBL was increased in mild PE (p ˂ 0.001) compared to controls. In conclusion, severe PE is characterized by altered expression of cytotoxic CD8(+) T cells in decidua and mPBL, suggesting their role in pathophysiology of PE and fetal-maternal immune tolerance.