Evaluation of Exhausted Regulatory T Cells in Preeclampsia

Document Type: Original Article

Authors

1 Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

2 Fertility, Infertility and Perinatology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

3 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

4 Department of Obstetrics and Gynecology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

Abstract

Background: The development of a maternal immune response to fetal antigens and deficiency in regulatory T-cells (Tregs) may lead to preeclampsia. A plausible explanation for the reduced Treg cell function in women with preeclampsia is the presence of exhausted Treg cells which express CD279 or programmed cell death receptor-1 (PD-1), a negative regulatory molecule associated with limited proliferative capacity and reduced immune suppression. Objective: To assess the number of Treg CD4+ CD25high and exhausted Treg CD4+ CD25high CD279+ cells in women with preeclampsia (PE group) and healthy pregnant women (HP group) during the third trimester of pregnancy. Methods: Three-color flow cytometry was used to determine the proportion of Treg and exhausted Treg cells in 40 women in the PE group and 37 women in the HP group. Participants’ blood samples were placed in EDTA blood collection tubes. Peripheral mononuclear cells were separated from the samples and stained with flurochrome-conjugated antibodies against human CD4, CD25 and CD279 markers, and subsequently analyzed by flow cytometry. Results: The PE group had fewer Tregs compared to the HP group (p=0.011). There was a significant increase in the percentage of exhausted PD-1+(CD279) Tregs (p=0.035) in the PE group comparisons with the HP group. Conclusion: The increased number of PD-1 (CD279) molecules on the Treg cells may play a role in preeclampsia, hence it recommendation as a therapeutic target for the disease.

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