CD8 and CD4 Positive NKT Subpopulations and Immune-Checkpoint Pathways in Early-Onset Preeclampsia and Healthy Pregnancy

Abstract

Although many studies have investigated the clinical aspect of early-onset preeclampsia, our knowledge about the immunological consequences of improper placenta development is scarce. The maternal immunotolerance against the fetus is greatly influenced by the Th1 predominance developed by the mother’s immune system. Thirty-two early-onset preeclamptic and fifty-one healthy pregnant women with appropriately matched gestational age were involved in our study. Mononuclear cells were separated from peripheral venous blood and the frequency of CD8⁺, CD4⁺, double positive (DP), and double negative (DN) NKT cell subpopulations was determined using multicolor flow cytometry. Following the characterization, the expression levels of different immune checkpoint receptors and ligands were also defined. Soluble CD226 levels were quantified by ELISA. Novel and significant differences were revealed among the ratios of the investigated NKT subsets and in the expression patterns of PD-1, LAG-3, TIGIT and CD226 receptors. Further differences were determined in the expression of CD112, PD-1, LAG-3 and CD226 MFI values between the early-onset preeclamptic and the healthy pregnant groups. Our results suggest that the investigated NKT subpopulations act differently in the altered immune condition characteristic of early-onset preeclampsia and indicate that the different subsets may contribute to the compensation or maintenance of Th1 predominance.

Keywords

• NKT
• immune checkpoint
• PD-1
• LAG-3
• TIGIT
• preeclampsia