Kinetics of regulatory T cells during murine pregnancy.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
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.
Thuere
Catharina
C
Institute of Medical Immunology, Charité, Universitätsmedizin, Berlin, Germany.
Zenclussen
Maria Laura
ML
Schumacher
Anne
A
Langwisch
Stefanie
S
Schulte-Wrede
Ursula
U
Teles
Ana
A
Paeschke
Steffen
S
Volk
Hans-Dieter
HD
Zenclussen
Ana Claudia
AC
D000034:Abortion, Veterinary / Q000201:enzymology / Q000276:immunology*; D000818:Animals; D003656:Decidua / Q000276:immunology; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism; D004970:Estrone / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000276:immunology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology* / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D004970:Estrone; D011374:Progesterone; D004958:Estradiol