Pregnancy‐associated diseases are characterized by the composition of the systemic regulatory T cell (T reg ) pool with distinct subsets of T regs

Summary Dysregulations concerning the composition and function of regulatory T cells (T regs ) are assumed to be involved in the pathophysiology of complicated pregnancies. We used six‐colour flow cytometric analysis to demonstrate that the total CD4 + CD127 low+/− CD25 + forkhead box protein 3 (FoxP3) + T reg cell pool contains four distinct T reg subsets: DR high+ CD45RA ‐ , DR low+ CD45RA ‐ , DR ‐ CD45RA ‐ T regs and naive DR ‐ CD45RA + T regs . During the normal course of pregnancy, the most prominent changes in the composition of the total T reg cell pool were observed between the 10th and 20th weeks of gestation, with a clear decrease in the percentage of DR high+ CD45RA ‐ and DR low+ CD45RA ‐ T regs and a clear increase in the percentage of naive DR ‐ CD45RA + T regs . After that time, the composition of the total T reg cell pool did not change significantly. Its suppressive activity remained stable during normally progressing pregnancy, but decreased significantly at term. Compared to healthy pregnancies the composition of the total T reg cell pool changed in the way that its percentage of naive DR ‐ CD45RA + T regs was reduced significantly in the presence of pre‐eclampsia and in the presence of preterm labour necessitating preterm delivery (PL). Interestingly, its percentage of DR high+ CD45RA ‐ and DR low+ CD45RA ‐ T regs was increased significantly in pregnancies affected by pre‐eclampsia, while PL was accompanied by a significantly increased percentage of DR ‐ CD45RA ‐ and DR low+ CD45RA ‐ T regs . The suppressive activity of the total T reg cell pool was diminished in both patient collectives. Hence, our findings propose that pre‐eclampsia and PL are characterized by homeostatic changes in the composition of the total T reg pool with distinct T reg subsets that were accompanied by a significant decrease of its suppressive activity.