Trafficking of T regulatory cells to the maternal-fetal interface
Pregnancy is an immunologic paradox:  How does the foreign fetus escape from maternal immune attack?  We, and others, have discovered that the mother uses T regulatory cells with specificity for the fetus to mediate immune tolerance.  Mechanistically, we are learning that the fetus plays an active role in changing the maternal Tregs in such a way that these cells are actively brought to the uteroplacental interface.  Once there, we know that they function to limit the maternal immune attack, but how?  Which cells are they interacting with?  Pregnancy provides a unique opportunity to learn about the fundamental biology of these important cells.   These studies are primarily being done using mice and advanced imaging.  

Preeclampsia as acute fetal rejection
Preeclampsia is a disease unique to human pregnancy.  The only cure is delivery, even when inflicting prematurity on the neonate.  The risk factors (first gestations, changes in paternity, extremes of reproductive age, concomitant autoimmune conditions) suggest an immunologic disorder as part of the fundamental pathology.  We are working on understanding the local factors the influence Treg : NK interactions at the uteroplacental interface during normal and preeclamptic pregnancies.  In addition, we are working on understanding if fundamental Treg functions are altered in preeclamptic pregnancies and why these women aren't all universally at risk for autoimmune disease.

 

Fetal response to maternal antigens  

The fetus has a robust immune system.  What is unique about the fetus is that they make overwhelmingly tolerance type of responses, mainly through Treg activation.  This kind of immune tolerance is long lasting (years).  Thus, if fetuses were to "experience" antigens to which an inflammatory response would be desirable later in life (e.g., infectious antigens), than in utero encounters could have long-lasting counter productive effects.  We are working on understanding the factors, both maternal and fetal, that alter antigen trafficking from the mother to her fetus.