Protective effect of progesterone substitution in pregnancy is mediated by Th2 cytokines and CD8+ cells

BLOIS SM; TOMETTEN M; GARCÍA MG; JOACHIM R; SZEKERES-BARTHO J; ARCK P

Malinska, Croacia

Congreso; The First EMBIC Summer School "Embryo implantation: from basics to clinics"; 2005

European Network of Excellence on Embryo Implantation Control (EMBIC)

Problem: One of the most remarkable immunological regulations is the maternal immune tolerance toward the fetal semi-allograft during pregnancy, which has been referred to as immunity’s pregnant pause. Cytotoxicity against the semi-allogeneic trophoblast cells must be selectively inhibited and pathways presumably include Th2 cytokines unopposed by Th1 cytokines. Steroid hormones, including progesterone, have similar effects. Low levels of progesterone and Th2 cytokines and high levels of Th1 cytokines are attributable for increased abortion in mammalians, which may be triggered by psychoemotional stress. Thus, the aim of the present study was to provide experimental evidence for the mechanism involved in the endocrine-immune bi-directionality during pregnancy and stress-triggered pregnancy failure. Method of Study: DBA/J-mated CBA/J female mice were randomized in three groups: 1) control females; 2) mice exposed to stress on gestation day (gd) 5.5 and 3) mice exposed to stress and substituted with the progesterone derivative dydrogesterone (gd 5.5). On gestation day 7.5 mice of each group were sacrificed, and the frequency of CD8+ cells and cytokine expression (IL-4, IL-12, TNF-a, IFN-g) in uterus cells was evaluated by flow cytometry. Additionally, some mice were depleted of CD8 cells by injection of monoclonal antibody. Results and Conclusions: We observed that progesterone substitution abrogated the abortogenic effects of stress exposure by decreasing the frequency of abortogenic cytokines. This pathway was exceedingly CD8-dependent, since depletion of CD8 led to a termination of the pregnancy-protective effect of progesterone substitution.