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

Violeta Soljic,Martina Vukoja,Maja Barbaric,Marina Curlin,Edita Cerni Obrdalj,Martina Orlovic Vlaho,Katarina Vukojevic,Daniela Bevanda Glibo,Lidija Lasic Arapovic

doi:10.3390/biology10101037

Violeta Soljic, Martina Vukoja + Show 7 more

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https://doi.org/10.3390/biology10101037

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Abstract

Simple SummaryCD8+ 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.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/mm2 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.

Highlights

Successful pregnancy outcome and fetal growth are highly dependent on the normal placental development and function
With the purpose to determine the localization of CD8+GNLY+, CD8+granzyme B (GzB)+, and CD8+ PRF1+ cells in decidua basalis, we analyzed paraffin-embedded placental tissue containing decidua basalis of both, PE and gestational age-matched control groups
The total number of PRF1+ cells/mm2, and CD8+PRF1+ cells/mm2 in decidua basalis of severe PE was significantly lower in comparison to the gestational age-matched control group (p < 0.0001; p < 0.01)

Summary

Introduction

Successful pregnancy outcome and fetal growth are highly dependent on the normal placental development and function. Incomplete and shallow invasion can lead to the development of pregnancy disorders, including intrauterine fetal growth restriction (IUGR), preterm labor, miscarriage, and, most commonly, PE [2,3]. There is no consistent and uniform classification of PE, but the one based on the severity of symptoms into mild and severe PE is commonly used [4,5,6]. Different forms of PE have significantly different clinical courses, outcomes, and, according to the latest data, pathophysiology [7,8]. Unpredictability is one of the common features of this disease, and what is at one moment a mild disease can very progress to severe PE which, regardless of the form, requires constant caution [4]

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