Specific Isolation of Placenta‐Derived Exosomes from the Circulation of Pregnant Women and Their Immunoregulatory Consequences1

作者：Anuradha Sabapatha, Cicek Gercel‐Taylor, Douglas D. Taylor · 发表于：American Journal of Reproductive Immunology · 年份：2006 · DOI：10.1111/j.1600-0897.2006.00435.x · 被引用次数：336 · 研究领域：Reproductive System and Pregnancy、Pregnancy and Medication Impact、COVID-19 Impact on Reproduction

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.