Kinetics of regulatory T cells during murine pregnancy.

PROBLEM: The semi-allogeneic fetus is usually tolerated by the maternal immune system. This was proposed to be modulated by CD4+CD25+foxp3+ regulatory T cells (Treg). We aimed to determine the kinetics of Treg during murine gestation and investigate whether changes in Treg levels respond to hormonal variations during pregnancy or generated changes in the local indolamine dioxygenase (IDO) expression. METHOD OF STUDY: We included in our studies the well-known CBA/JxDBA/2J abortion-prone combination using CBA/JxBALB/c as controls. CBA/JxC57/BL6 and BALB/cxC57/BL6 were included as further controls. Animals were killed on days 0, 2, 5, 8, 10, and 12 of pregnancy to measure the levels of Treg, pregnancy-related hormones and IDO expression. RESULTS: A Treg augmentation in normal pregnancy combinations could be observed on day 2 in several organs contrary to the observations made in abortion-prone mice. No differences in hormonal levels could be seen among all groups. IDO was expressed exclusively in placenta starting from day eight, showing no variations among the groups. CONCLUSION: Differences in Treg levels and pregnancy outcome do not correlate with changes in hormonal levels. In addition, as Treg augmentation takes place early and it is observed mainly in the decidual component of the fetal-maternal interface, IDO does not seem to be the pathway underlying Treg protective activity as proposed for humans.

Pre-eclampsia is not associated with changes in the levels of regulatory T cells in peripheral blood.

PROBLEM: The acceptance of the semi-allogeneic fetus within the maternal environment requires tolerance mechanisms not fully characterized yet. Normal pregnancy is known to be associated with a Th2 profile. Furthermore, regulatory T cells (Tregs) were proposed to regulate the Th2/Th1 balance at early stages of pregnancy. Treg may avoid the shift to a Th1 profile, thus preventing miscarriage. Accordingly, spontaneous abortion is characterized by a Th1 dominance and diminished levels of Treg. The major aim of the present work was to investigate if pre-eclampsia, a late immunological complication of pregnancy, is characterized by similar hallmarks. METHOD OF STUDY: We measured the surface antigens CD4, CD25, CD8 and CTLA4 in peripheral blood from patients suffering from pre-eclampsia (n = 8) and age-matched patients undergoing normal pregnancies (n = 9) by four-color flow cytometry. RESULTS: We were not able to find any significant differences in the levels of CD4(+), CD25(+), CD8(+), CTLA4, CD4(+)/CD25(+), CD4(+)/CD25(bright), CD4(+)/CTLA4, CD25(+)/CTLA4, CD4(+)/CD25(+)/CTLA4, CD8(+)/CD25(+), CD8(+)/CTLA4 or CD8(+)/CD25(+)/CTLA4 cell subsets. CONCLUSIONS: Our data confirm comparable number of Tregs during pre-eclampsia and normal pregnancy in peripheral blood. Other regulatory mechanisms might be involved during late pregnancy.