Distinct subsets of regulatory T cells during pregnancy: Is the imbalance of these subsets involved in the pathogenesis of preeclampsia?

Regulatory T cells (CD4+CD25+FoxP3+-Treg cells) are important regulators of tolerance induction during pregnancy. We now found that the number of CD4+CD25+FoxP3+-Treg cells decreases during normal course of pregnancy and even more so in women affected by preeclampsia. The functional activity of these CD4+CD25+-Treg cells was significantly reduced in comparison to those of healthy pregnants. Further analysis revealed two Treg subsets that differed with regard to the FoxP3 and CD25 expression. The percentage of both, CD4+CD25+FoxP3high+-Treg and CD4+CD25high+FoxP3+, was maximal in the first and second trimenon, but declined severely in the third trimenon. In preeclamptic women the population of CD4+CD25high+FoxP3+-Treg cells was particularly apparent, while the population of CD4+CD25+FoxP3high+-Treg cells was significantly decreased. We propose that CD4+CD25+FoxP3high+- and CD4+CD25high+FoxP3+-Treg cell populations represent distinct Treg cell subsets, and that disturbances in the balance of these two Treg cell subsets are associated with the presence of preeclampsia, but not HELLP-syndrome.