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Expert Rev Clin Immunol. 2016;12(2):209-27. doi: 10.1586/1744666X.2016.1105740. Epub 2015 Nov 18.

Regulatory T-cells and preeclampsia: an overview of literature.

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a Department of Biochemistry, Faculty of Medicine , Hormozgan University of Medical Sciences , Bandar Abbas, Iran.
c Molecular Medicine Research Center , Hormozgan University of Medical Sciences , Bandar Abbas , Iran.
b Department of Immunology, Faculty of Medicine , Hormozgan University of Medical Sciences , Bandar Abbas , Iran.


Regulatory T-cells (Tregs) are key players in successful pregnancy and their deficiencies are implicated in pregnancy complications such as preeclampsia (PE), but the results are inconsistent among studies. This study aims to compile an overview of the studies about the associations of Tregs and PE risk and to provide recommendations for future research. A sensitive search of three databases including PubMed, Scopus and Google scholar (from 1995 to January 9, 2015) identified 636 unique titles. An accurate process of study selection, data extraction and method qualification were independently conducted by authors on retrieved papers. Seventeen papers met the inclusion criteria and were included in quality assessment. Regarding the source of Tregs, 14 studies assessed Tregs in peripheral blood, 2 studies in peripheral blood and decidua and one study in peripheral blood and umbilical cord blood. Despite variation in the combinations of markers and other aspects of the studies designs, remarkable constancy in the results of studies that measured Tregs as CD4+FoxP3+ or CD4+CD25+FoxP3+ cells (but not CD4+CD25(high/low)FoxP3+ markers) was found, which in broad terms showed a shift towards fewer Treg cells in PE. This review revealed an association between lower percentage of circulating CD4+FoxP3+ or CD4+CD25+FoxP3+ Tregs and the risk of PE. Given the above issue and regarding the high consistency of studies on reduction of suppressive activity of Tregs in PE, we have proposed a model in which the Tregs deficiency is a reflection of immune endocrine imbalance, which reverses maternal tolerance and results in development of preeclampsia.


Immune tolerance; preeclampsia; pregnancy; regulatory T-cell; systematic review

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