Oral Presentation 6th Australian Health and Medical Research Congress 2012

The Placenta: The Source of Immune Suppression in Pregnancy? (#108)

Sharon A McCracken 1
  1. Sydney University, St Leonards, NSW, Australia

During normal pregnancy Th1 immune responses, which mediate acute allograft rejection, are significantly suppressed. The mechanisms that mediate this suppression are unknown. Our group has identified an essential role for the Th1 transcription factor NF-κB (p65) in controlling the cytokine environment throughout pregnancy. We have shown that p65 is specifically suppressed in T-cells in pregnancy from as early as the first trimester. We have also demonstrated a pivotal role for p65 in regulating T-bet, the Th1 master controller thus in turn regulating Th1 cytokine production. The suppression of p65 in T-cells can be induced by maternal plasma and serum and involves factor(s) present in the particulate fraction as ultracentrifugation removes the suppressive properties. Throughout gestation particulate “debris” is released from the placenta and shed into the maternal circulation. Debris includes large multinucleated syncytial knots, individual trophoblast and smaller membranous microparticles (STBMs). However, in addition to debris the placenta actively releases nanometer sized microvesicles called exosomes. Exosomes are produced by almost all cells in the body. The placenta produces large amounts of exosomes and they have been shown to play a pivotal role in fetal-maternal cross talk specifically through altering effector T-cell function. Placental exosomes have been shown to express FasL. It has been shown that the interaction between FasL and its cognate receptor (Fas) mediates the immunosuppressive function of these vesicles. Fas activation has been shown to result in caspase-mediate degradation of p65. We have shown that by inhibiting Fas interaction between T-cells and maternal plasma or placental exosomes we can inhibit p65 suppression. Thus placental exosomes are potential mediators of the immune suppression required for regulating the maternal environment necessary for pregnancy success.