Journal Article

First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis

Vikki M. Abrahams, Shawn L. Straszewski‐Chavez, Seth Guller and Gil Mor

in MHR: Basic science of reproductive medicine

Published on behalf of European Society of Human Reproduction and Embryology

Volume 10, issue 1, pages 55-63
Published in print January 2004 | ISSN: 1360-9947
Published online January 2004 | e-ISSN: 1460-2407 | DOI: https://dx.doi.org/10.1093/molehr/gah006
First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis

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Since the invading trophoblast represents a semi‐allograft, it should be rejected by the mother. It has, therefore, been postulated that during normal pregnancy the trophoblast evades the maternal immune system though the establishment of immune privilege by triggering the death of activated lymphocytes which may be sensitized to paternal alloantigens. Such peripheral tolerance may be directed through the Fas/Fas ligand (FasL) apoptotic pathway and mediated by FasL expressed by the trophoblast. However, in vivo studies show that membrane‐associated expression of FasL may instead promote allograft rejection, rather than protection. The aim of this study was to determine if there is a role for FasL in trophoblast immune privilege. In this study, we demonstrate that isolated first trimester trophoblast cells lack membrane‐associated FasL, but express a cytoplasmic form in association with a specialized secretory lysosomal pathway. Furthermore, this intracellular FasL is constitutively secreted by trophoblast cells via the release of microvesicles. Following disruption of these microvesicles, the whole 37 kDa secreted FasL is able to induce T‐cell death by apoptosis through activation of the Fas pathway. Therefore, we propose that secretion of FasL may be one mechanism by which trophoblast cells promote a state of immune privilege and, therefore, protect themselves from maternal immune recognition.

Keywords: Key words: FasL/immune privilege/implantation/microvesicle/trophoblast

Journal Article.  7391 words.  Illustrated.

Subjects: Reproductive Medicine

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