Cell death mechanisms and potentially cytotoxic natural immune cells in human pregnancies complicated by preeclampsia

Reprod Sci. 2014 Feb;21(2):155-66. doi: 10.1177/1933719113497288. Epub 2013 Jul 24.

Abstract

Preeclampsia, which occurs in about 2% to 3% of all pregnancies, is a severe multisystem disorder showing symptoms in the second half of human pregnancy. Its prevention, early diagnosis, and treatment are insufficient, since etiology and pathogenesis of the disease are still not totally understood. Recent studies confirm that preeclampsia is the extreme end of a normal inflammatory reaction, which also occurs in healthy pregnancies. This review focuses on maternal immune changes during preeclampsia leading to altered cytotoxic responses. The potential role of perforin/granzyme-, Fas/Fas-ligand-, tumor necrosis factor α (TNF-α)- or TNF-related apoptosis-inducing ligand-mediated apoptotic mechanisms in the pathomechanism is analyzed. The frequency and function of effector cytotoxic cells of natural immunity itself such as natural killer (NK) cells, NKT cells, and γδT cells are also changed both in the periphery and locally in the uterus influencing the outcome of pregnancy. Here, authors conclude that beside exaggerated inflammatory responses, apoptotic and killing mechanisms also seem to be implicated in the pathogenesis of preeclampsia.

Keywords: NK cells; NKT cells; cytotoxicity; preeclampsia; γδT cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Death / immunology
  • Cytotoxicity, Immunologic / immunology*
  • Fas Ligand Protein / immunology
  • Female
  • Humans
  • Killer Cells, Natural / immunology
  • Pre-Eclampsia / diagnosis*
  • Pre-Eclampsia / immunology*
  • Pregnancy
  • TNF-Related Apoptosis-Inducing Ligand / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Fas Ligand Protein
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha