Human HLA-G+ extravillous trophoblasts: immune activating cells that interact with decidual leucocytes (MUC2P.921)

Abstract

Abstract Invading HLA-G+ extravillous trophoblasts (EVT) are believed to play a key role in the prevention of a maternal immune attack on foreign fetal tissues. EVT are difficult to study due to their low frequency and lack of proliferative capacity. Here highly purified HLA-G+ EVT and HLA-G- villous trophoblast (VT) were isolated. Culture on fibronectin increased HLA-G expression on EVT but differentiation from VT into EVT was not observed. Moreover microarray analysis demonstrated that VT and EVT have more than 4200 differentially expressed genes. Functional gene set enrichment analysis (GSEA) revealed a striking immune activating potential for EVT that is absent in VT. Co-culture of HLA-G+ EVT with sample matched decidual NK, macrophages, CD4+ and CD8+ T cells were established and demonstrated interactions of all leukocyte types with EVT. Interaction of EVT with CD4+ T cells resulted in increased proportion of CD4+CD25hiFOXP3+ Tregs and increased FOXP3 protein level in these cells. However, EVT did not enhance cytokine secretion in dNK whereas stimulation of dNK using mitogens or classical NK targets confirmed the distinct cytokine profiles of dNK and pNK. Thus EVT are specialized cells with an immune activating profile whose properties are not imitated by HLA-G expressing cell lines. Careful validation of EVT-leukocyte interactions using primary HLA-G+ EVT needs to be carried out to understand the unique contribution of EVT to the decidual immune response in human pregnancy.