Physiological role of IL-15 and IL-18 at the maternal-fetal interface.

We review recent studies of two cytokines IL-15 and IL-18, showing that they are the critical cytokines controlling uterine NK cell cytokine production and cytolytic potential. Further, IL-15 has been implicated in differentiation and proliferation of uterine NK cells, while IL-18 enhanced innate immunity and both Th1- and Th2-driven immune responses depending on the cytokine milieu. We addressed the possible role of these two cytokines in induction of the IFN-gamma production as a key molecule in vascular remodeling during early pregnancy.

Perforin and Fas/FasL cytolytic pathways at the maternal-fetal interface.

The immunogenetic enigma of maternal acceptance of the fetal semiallograft has been termed an immunological paradox. The first trimester decidua is heavily infiltrated with CD56(bright) CD16- uterine natural killer (uNK) cells which must be prepared to respond to potential pathogen challenges and still be able to control immune responses that allow the development of the fetus. The significant presence of cytolytic mediators, perforin and Fas/Fas ligand (FasL), at the maternal-fetal interface raises a question of their role(s) in the immunological interrelations between maternal tissues and trophoblast cells. As uNK cells in vitro lyse target cell lines (K562, P815 and P815Fas) using these effector molecules, it seems that, although immunocompetent, their cytotoxicity is not directed against trophoblast during normal pregnancy. Therefore, it is generally believed that the hormonal and Th1/Th2 cytokine balance plays an important role in the tolerance and maintenance of pregnancy. This paper gives an overview of the recent findings on the complex immunological events that occur at the maternal-fetal interface.

An insight into the dendritic cells at the maternal-fetal interface.

The conditions that permit the genetically distinct fetus to survive and develop within the mother are among the most fascinating immunologic puzzles. The presence of dendritic cells in the maternal decidua pointed to a biologic role of antigen-presenting cells in maternal-fetal interaction. The method of study included recent findings on the lineage, maturity, phenotype and function of dendritic cells at the maternal-fetal interface. The increment of uterine dendritic cells occurs simultaneously with the decisive phase of gestation, when implantation takes place. Decidual dendritic cells of the first trimester pregnancy, with a phenotype characteristic of the mature myeloid lineage, express MHC class II, co-stimulatory and adhesion molecules, control Th1/Th2 balance and activate the proliferative response of autologous NK cells. Dendritic cells are specifically equipped to control immunity, to trigger immune response and also to maintain tolerance, avoiding the rejection of the conceptus by the maternal immune system.