Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes

Tamara Tilburgs, Ângela C. Crespo, Anita Van Der Zwan, Basya Rybalov, Towfique Raj, Barbara Stranger, Lucy Gardner, Ashley Moffett, Jack L. Strominger

Research output: Contribution to journalArticlepeer-review

155 Scopus citations


Invading human leukocyte antigen-G+ (HLA-G+) extravillous trophoblasts (EVT) are rare cells that are believed to play a key role in the prevention of a maternal immune attack on foreign fetal tissues. Here highly purified HLA-G+ EVT and HLA-G. villous trophoblasts (VT) were isolated. Culture on fibronectin that EVT encounter on invading the uterus increased HLA-G, EGF-Receptor-2, and LIFReceptor expression on EVT, presumably representing a further differentiation state. Microarray and functional gene set enrichment analysis revealed a striking immune-activating potential for EVT that was absent in VT. Cocultures of HLA-G+ EVT with sample matched decidual natural killer cells (dNK), macrophages, and CD4+ and CD8+ T cells were established. Interaction of EVT with CD4+ T cells resulted in increased numbers of CD4+CD25HIFOXP3+CD45RA+ resting regulatory T cells (Treg) and increased the expression level of the Treg-specific transcription factor FOXP3 in these cells. However, EVT did not enhance cytokine secretion in dNK, whereas stimulation of dNK with mitogens or classical natural killer targets confirmed the distinct cytokine secretion profiles of dNK and peripheral blood NK cells (pNK). EVT are specialized cells involved in maternal.fetal tolerance, the properties of which are not imitated by HLA-G.expressing surrogate cell lines.

Original languageEnglish
Pages (from-to)7219-7224
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - 9 Jun 2015
Externally publishedYes


  • FOXP3
  • Human
  • NK cell
  • Pregnancy
  • Treg


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