Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences

Am J Reprod Immunol. Nov-Dec 2006;56(5-6):345-55. doi: 10.1111/j.1600-0897.2006.00435.x.

Abstract

Problem: One immunoregulatory pathway receiving little attention is placental exosome release. In normal pregnancy, as factors linked with early immunomodulation decline, placental exosomes become critical in modulating T-cell activation, suppressing effector T cells by enhancing lymphocyte apoptosis and CD3-zeta loss.

Method of study: Placental exosomes were specifically isolated from the maternal peripheral circulation by a chromatographic/immunosorbent procedure. Exosomal suppression of T-cell signaling molecules on unfractionated T cells and T subsets was analyzed by Western immunoblot. The role of Fas ligand (FasL) was defined by use of Fas-blocking antibody.

Results: While exosomes of lymphoid origin could be demonstrated in all women, placenta-derived exosomes were only identified in pregnant patients. Placental exosomes suppressed T-cell expression of CD3-zeta and JAK3, while inducing SOCS-2. This downregulation of CD3-zeta was partially reversed by pre-incubating T cells with ZB4 antibody. Using T subsets, the level of CD3-zeta on CD8+ cells was inhibited 1.43-fold more than in CD4+ cells. On CD4+ CD25+ cells, CD3-zeta was not significantly inhibited.

Conclusion: Placental exosomes suppressed T-cell signaling components; however, while exosomal FasL is an important contributor, it does not appear to be the sole mediator. The additional expression of PD-L1 may explain immunoregulatory consequences of exosomes with low or absent FasL.

MeSH terms

  • Adult
  • Antigens, CD / immunology
  • Apoptosis
  • Exocytosis*
  • Female
  • Humans
  • Placenta / cytology*
  • Placenta / immunology*
  • Pregnancy / blood*
  • Pregnancy / immunology*
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD