Regulatory T-cells and preeclampsia: an overview of literature

Abstract

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/lowFoxP3+ 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.

Keywords:

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

Acknowledgements

We thank Dr Ali Montazeri, Dr Afshin Samiei and Dr Maryam Tavakoli for their valuable comments on drafts of this review.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• PE is a leading cause of maternal and perinatal morbidity and mortality which is characterized by hypertension and proteinuria in the second half of pregnancy in a previously normotensive woman.

• Abundant evidences suggest that immunological factors such as the predominance of a Th1-type immunity and pro-inflammatory cytokines are crucial for the development of this disease.

• Tregs are regarded as having an important role in regulating the immune response and tolerance to the fetus.

• Changes of Treg cell number and function in PE still remain a controversial issue.

• This systematic review revealed an association between lower percentage of Tregs and lower suppressive activity of Tregs and the risk of PE.

• It is likely that immunotherapy based on Treg can be beneficial in the treatment of PE.