Introducing a mouse model for pre-eclampsia: adoptive transfer of activated Th1 cells leads to pre-eclampsia-like symptoms exclusively in pregnant mice

Eur J Immunol. 2004 Feb;34(2):377-87. doi: 10.1002/eji.200324469.

Abstract

Pre-eclampsia (PE) is the most severe pregnancy-related disease, leading to high maternal and fetal morbidity/mortality. Immunological imbalances associated with endothelial cell dysfunction have been hypothesized as a cause for the onset and perpetuation of PE. Valid and reliable animal models are urgently required to test this hypothesis and to better understand the mechanisms underlying PE. We developed a novel PE-model by adoptively transferring activated BALB/c Th1-like splenocytes into allogeneically pregnant BALB/c female mice during late gestation; the model mimicked the symptoms of PE, i.e. increased blood pressure and glomerulonephritis accompanied by proteinuria. Interestingly, these PE-like symptoms were not detectable in non-pregnant recipients of activated Th1-like cells. Adoptive cell transfer adversely affected the outcome of pregnancy by increasing fetal rejection, with uterine immune cells showing an inflammatory profile. In conclusion, we have established a valid and reliable PE mouse model, which opens vast opportunities for therapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Blood Pressure
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Pre-Eclampsia / immunology*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Proteinuria
  • Random Allocation
  • Receptors, CCR5 / blood
  • Th1 Cells / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism
  • Uterus / immunology
  • Uterus / pathology

Substances

  • Receptors, CCR5
  • Tumor Necrosis Factor-alpha
  • Interleukin-12