title: Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Sabapatha
authors.forename: Cicek
authors.initials: C
authors.lastname: Gercel-Taylor
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Taylor
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis; D005089:Exocytosis; D005260:Female; D006801:Humans; D010920:Placenta / Q000166:cytology* / Q000276:immunology*; D011247:Pregnancy / Q000097:blood* / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD