Lineage, maturity and phenotype of dendritic cells at human and murine maternal-fetal interface

PROBLEM: Dendritic cells (DCs) are the crucial components of the immune system and the most potent activators of naive T-lymphocytes, as well as the modulators of B and natural killer (NK) cell responses. DCs sample, trap, engulf and digest various antigens, what is known as antigen processing, owing to their strategic emplacement at the boundaries between the inner and the outside world, in a way bridging innate and acquired immunity. Rapid accumulation of DC precursors in inflamed tissues upon pathogen invasion is a result of their recruitment from the blood, in response to the chemokines produced at the inflammation site. Only limited information is available about DCs role in pregnancy, but they are thought to be involved in the regulatory functions, balancing immune response towards tolerance or immunity. In this study we analyzed presence, distribution, origin and function of DCs in normal human first trimester pregnancy decidua and uterine DC subsets in mice. METHODS: Experiments were performed on freshly isolated and/or cultured decidual mononuclear cells (DMCs) of normal human first trimester decidual tissue, obtained by elective pregnancy terminations, and uterine cells of adult C57Bl/6 female mice mated with syngenic C57Bl/6 (C57Bl/6xC57Bl/6) and allogenic BALB/c (C57Bl/6xBALB/c) males. Lineage, maturity, phenotype and endocytosis of DCs were detected by flow cytometry and immunohistochemistry method. Human CD83+ cells and murine CD11c+ cells were purified by magnetic beads and used in CFSE proliferation assays. Besides in uteri, frequency of CD11c+ cells, as well as intracellular staining of IFN-g, were also investigated in the spleen and lymph nodes of pregnant animals. RESULTS: Decidual CD83+ cells up-regulate HLA-DR and CD86, while they down-regulate mannose receptor (CD206) after overnight culture. Endocytic activity of CD83+ cells was measured by uptake of FITC-dextran and they efficiently took up antigen. After 96 hours cultivation with purified CD83+ cells, an increased proliferation rate of decidual NK (CD56+) cells was obtained. In both syngenic and allogenic murine pregnancy model (4 day of gestation), number of uterine CD11c+ cells was increased and the expression of CD86 and MHC class II (I-Ab) molecules on their surface was up-regulated, compared to the virgin ones. Both human and murine DCs are of myeloid origin and they can stimulate NK cells (human CD56+ and murine DX5+) to produce IFN-g. CONCLUSIONS: At the maternal-fetal interface, human (CD11chighCD123low) and murine (CD11c+CD8-) DCs are of myeloid origin, express high amounts of co-stimulatory and MHC class II molecules and are capable of activating decidual NK cells.