Decreased ratio of FOXP3/FOXP3CD45RACD4 T cells in peripheral blood is associated with unexplained infertility and ART failure.

Unexplained infertility has a huge social impact and is a significant challenge for both clinicians and researchers. Previous studies have shown the involvement of multiple factors in infertility. Among these, the subset of regulatory T cells is of particular interest for the maternal tolerance towards the semi-allogenic fetus. We investigated circulating CD45RA regulatory and non-regulatory CD4 T cells in healthy women and patients with unexplained infertility in the context of thymic output and peripheral proliferation. The proportion of FOXP3 and FOXP3CD45RACD4 T cells in peripheral blood was studied in control groups of healthy parous and nulliparous (never-pregnant) women and in patients with unexplained infertility. In the same groups thymic output and peripheral proliferation were defined by the sj/βTREC ratio, and signal joint T-cell receptor excision circles (sjTREC) and Ki67 expression, respectively. In parous women a decrease in sjTREC/10 cells and CD45RA T lymphocytes, compared to nulliparous group was found. At the same time, the proportion of FOXP3CD45RACD4 cells, but not FOXP3CD45RA Tregs was reduced. In contrast, in patients with unsuccessful pregnancy, proportions of both regulatory and non-regulatory T cell counterparts were lower. Taken together, our results provide evidence for group-specific properties in the CD45RA T cell compartment between healthy parous, nulliparous and women with unexplained infertility.