Expansion of CD4+HLA-G+ T Cell in Human Pregnancy is Impaired in Pre-eclampsia

• Published in: American journal of reproductive immunology (1989) 2014-03, Vol.71 (3), p.217-228
• Main Authors: Hsu, Peter, Santner-Nanan, Brigitte, Joung, Steven, Peek, Michael J., Nanan, Ralph
• Format: Article
• Language: English
• Subjects: Adult; Blood Cells - immunology; CD4 Antigens - metabolism; CD4+HLA-G+ T cells; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cell Proliferation; Coculture Techniques; Decidua - immunology; Dendritic Cells - immunology; Endocytosis - immunology; Female; HLA-G Antigens - genetics; HLA-G Antigens - metabolism; human pregnancy; Humans; Immune Tolerance; Interleukin-10 - immunology; Lectins, C-Type - genetics; Lectins, C-Type - metabolism; Lipopolysaccharide Receptors - metabolism; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Pre-Eclampsia - immunology; Pregnancy; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Immunologic - genetics; Receptors, Immunologic - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology; Up-Regulation; Young Adult
• ISSN: 1046-7408; 1600-0897
• DOI: 10.1111/aji.12195

Problem The role of CD4+HLA‐G+ T cells in healthy pregnancy and pre‐eclampsia is unclear. Method of study CD4+HLA‐G+ T cells were analysed from peripheral blood and decidual samples from healthy pregnant and pre‐eclamptic women. In vitro T‐cell induction, trogocytosis and suppression assays were performed. Results In peripheral blood, CD4+HLA‐G+ T cells were significantly higher in pregnant women (mean ± S.E.M.: 7.98 ± 1.10%), compared with non‐pregnant controls (mean ± S.E.M.: 1.78 ± 0.30%) and pre‐eclamptic women (mean ± S.E.M.: 3.69 ± 0.51%). The presence of CD4+HLA‐G+ T cells is even more prominent in the decidua, suggestive of local induction and accumulation. Decidual CD14+DC‐SIGN+ antigen‐presenting cells (APCs) enhance the HLA‐G expression of cocultured CD4+ naïve T cells in vitro. IL‐10 augments expression of HLA‐G, ILT4 and DC‐SIGN in monocyte‐derived DCs (MoDCs), endowing them with a phenotype analogous to decidual CD14+DC‐SIGN+ APCs of healthy pregnancy. Furthermore, naïve T cells acquire HLA‐G from these IL‐10‐treated MoDCs via the process of trogocytosis. Conclusions Our data indicate that in addition to Foxp3+ Treg cells, CD4+ T cells acquire HLA‐G from decidual DCs and may play an important role in immune tolerance induction in pregnancy, a process which is impaired in pre‐eclampsia.