Proportional changes of CD4+CD25+Foxp3+ regulatory T cells in maternal peripheral blood during pregnancy and labor at term and preterm.

PURPOSE To evaluate the proportional changes of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in maternal peripheral blood during pregnancy and labor at term and preterm. METHODS Peripheral blood was collected from 20 non-pregnant controls and 139 pregnant women (60 at different gestational ages, 48 at term with or without labor, and 31 in threatened or actual preterm labor). CD4+CD25+Foxp3+ Tregs in peripheral blood samples were analyzed in peripheral blood samples by flow cytometry. Placentas from preterm women were examined for the presence of histological chorioamnionitis (HC). RESULTS The percentage of circulating CD4+CD25+Foxp3+ Tregs was significantly increased in women during the first trimester compared with non-pregnant controls (P < 0.0001), peaking during the second trimester and then declining slightly in the third trimester. There was a significantly lower level of CD4+CD25+Foxp3+ Tregs in women with term labor than in those at term without labor (P < 0.0001). Women admitted in preterm labor had a lower proportion of CD4+CD25+Foxp3+ cells than those admitted with threatening preterm labor (P < 0.0001). Preterm women with evidence of HC had decreased proportion of CD4+CD25+Foxp3+ cells than those without HC in preterm deliveries (P=0.008). Moreover, the percentages of CD4+CD25+Foxp3+ cells in preterm subjects, irrespective of the HC status, were significantly diminished compared with women with normal pregnancy at the same gestational age (P < 0.0001). CONCLUSION Our data reveal a marked elevation of peripheral blood CD4+CD25+Foxp3+ Tregs during early pregnancy, but a dramatic decline during labor, either at term or preterm, suggesting their involvement in the maintenance of pregnancy and the initiation of labor.