PD1+ T Regulatory Cells Are Not Sufficient to Protect from Gestational Hypertension

Tolerance to foetal tissues in pregnancy depends on the match between mother and child. CD4+Foxp3+ regulatory T cells (Tregs), which are involved in peripheral tolerance, may facilitate this effect. Previous findings have indicated that the number of missing KIR ligands (MSLs) between mother and child correlates with the risk of gestational hypertension (GH) and preeclampsia (PE). This study tested whether Tregs are involved in the pathogenesis of gestational disorders. In total, 57 pregnant women participated, including 39 with hypertensive disorders of pregnancy and 18 healthy controls. Treg phenotypes were evaluated using multicolour flow cytometry. Killer cell immunoglobulin-like receptors (KIRs) and their ligands were assessed using NGS and PCR-SSO typing. The correlation between the MSLs and Treg antigen expression was evaluated. The pregnancy-related hypertensive groups differ from the healthy control group in the frequency of particular Treg subsets. However, there was a correlation between an increasing number of MSLs and only one subset of Tregs, which was PD-1+ Tregs. Surprisingly, women suffering from GH or PE had a significantly higher percentage of PD-1+ Tregs than healthy pregnant women. The percentages of several other populations of Tregs, such as those expressing CCR4, CCR10, CD39, and CD73, were higher in healthy pregnant women than in those with GH or PE, but these numbers did not correlate with MSLs. The exhausted PD-1+ Treg cell subsets may play a crucial role in the pathogenesis of hypertensive disorders of pregnancy. It is also hypothesised that MSLrelated mechanisms trigger PD-1+ Treg expansion, but their increased number fails to provide protection against hypertensive conditions of pregnancy.