Incomplete activation of peripheral blood dendritic cells during healthy human pregnancy

• Published in: Clinical and experimental immunology Vol. 164; no. 2; pp. 180 - 192
• Main Authors: Della Bella, S., Giannelli, S., Cozzi, V., Signorelli, V., Cappelletti, M., Cetin, I., Villa, M. L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2011; Blackwell; Blackwell Science Inc
• Subjects: Activins - pharmacology; Activins - physiology; activin‐A; Adaptations; Adult; Analytical, structural and metabolic biochemistry; Antigen Presentation; Biological and medical sciences; Cell activation; Cell culture; Cells, Cultured - drug effects; Cells, Cultured - immunology; co‐stimulatory molecules; Cytokines; Cytokines - biosynthesis; Cytokines - classification; Cytokines - genetics; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Female; Fetuses; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Glycoproteins; Histocompatibility antigen HLA; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - genetics; HLA‐DR; Hormones; Humans; Immune response; Immune system; Immune Tolerance - immunology; Immunological tolerance; Inflammation; Leukocytes; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; Lymphocyte Culture Test, Mixed; Maternal-Fetal Exchange; Peripheral blood; Pregnancy; Pregnancy Trimester, Third; Recombinant Proteins - pharmacology; Translational Studies; Up-Regulation; Uterus; Young Adult; Human; co-stimulatory molecules; Dendritic cell; HLA-System; Activin A; Class II histocompatibility antigen; Cytokine; Activation; Biochemistry; activin-A; HLA-DR-Locus; peripheral blood; Costimulatory molecule; Blood; Pregnancy; Blood cell; dendritic cells; HLA-DR; Antigen presenting cell; Female; cytokines
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2011.04330.x

Summary Successful pregnancy relies on the adaptation of immune responses that allow the fetus to grow and develop in the uterus despite being recognized by maternal immune cells. Dendritic cells (DCs) are central to the control of immune tolerance, and their state of activation at the maternal–decidual interface is critical to the feto–maternal immunological equilibrium. So far, the involvement of circulating DCs has been investigated poorly. Therefore, in this study we investigated whether, during healthy human pregnancy, peripheral blood DCs (PBDCs) undergo changes that may be relevant to the adaptation of maternal immune responses that allow fetal tolerance. In a cross‐sectional study, we analysed PBDCs by six‐colour flow cytometry on whole blood samples from 47 women during healthy pregnancy progression and 24 non‐pregnant controls. We demonstrated that both myeloid and plasmacytoid PBDCs undergo a state of incomplete activation, more evident in the third trimester, characterized by increased expression of co‐stimulatory molecules and cytokine production but lacking human leucocyte antigen (HLA)‐DR up‐regulation. To investigate the contribution of soluble circulating factors to this phenomenon, we also performed culture experiments showing that sera from pregnant women added to control DCs conditioned a similar incomplete activation that was associated with reduced DC allostimulatory capacity, supporting the in vivo relevance of our findings. We also obtained evidence that the glycoprotein hormone activin‐A may contribute to DC incomplete activation. We suggest that the changes of PBDCs occurring during late pregnancy may aid the comprehension of the immune mechanisms operated by the maternal immune system to maintain fetal tolerance.