Introducing a mouse model for pre-eclampsia: adoptive transfer of activated Th1 cells leads to pre-eclampsia-like symptoms exclusively in pregnant mice.
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.
Zenclussen
Ana C
AC
Biomedizinisches Forschungszentrum, Charité, Campus Virchow Klinikum, Humboldt University, Berlin, Germany.
Fest
Stefan
S
Joachim
Ricarda
R
Klapp
Burghard F
BF
Arck
Petra C
PC
D019264:Adoptive Transfer; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D011225:Pre-Eclampsia / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D011507:Proteinuria; D011897:Random Allocation; D019713:Receptors, CCR5 / Q000097:blood; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014599:Uterus / Q000276:immunology / Q000473:pathology
D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12