Article

Differential expression of TcR-CD3 zeta as evidence for altered immunoregulation in preeclamptic versus normotensive women

Division of Gynecology Oncology, University of Louisville, Louisville, Kentucky, United States
American Journal of Obstetrics and Gynecology (Impact Factor: 3.97). 09/2003; 189(3):843-7. DOI: 10.1067/S0002-9378(03)00815-9
Source: PubMed

ABSTRACT The study was undertaken to exhibit and quantify the difference in modulation of CD3-zeta protein (an integral component of the T-cell receptor) in preeclamptic and normotensive women.
Serum was collected from 10 preeclamptic and 10 normotensive women at >or=37 weeks' gestation on admission. Jurkat E-61 cells were incubated with the sera (20% volume to volume) and analyzed with Western immunoblot using mouse monoclonal CD3-zeta antibody. Enhanced chemiluminescence and densitometry were used to qualitatively measure zeta expression of the cells. A de novo flow cytometry assay was developed to quantify the difference in CD3-zeta expression of these cells. Comparisons were performed by t test (P<.05 was significant).
Preeclamptic patient sera produced a 2.4-fold increase in CD3-zeta expression than normotensive patients on Western blot (P<.01). Flow cytometry showed that preeclamptic sera had a 1.4-fold higher expression of CD3-zeta compared with normotensive patients (P<.0003).
TcR/CD3-zeta expression is normally suppressed in pregnancy. Loss of this suppression occurs in preeclamptic patients, implying increased T-cell function.

0 Followers
 · 
44 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cellular microparticles are ubiquitously shed from cell membranes or secreted as endocytic vesicles called exosomes. Shed microparticles are >/=100nm in size and are generated during apoptosis or necrosis. In contrast, exosomes are smaller (<100nm), express more limited protein content and are released from late endosomes. Both membrane particles and exosomes can be detected in the circulation in non-pregnant and pregnant women. In the former, they are increased in conditions associated with systemic inflammation such as sepsis or metabolic syndrome. During pregnancy, they are also associated with pre-eclampsia and include not only particles derived from platelets, endothelium and various leukocytes but also syncytiotrophoblast-derived microparticles. Syncytiotrophoblast membrane microparticles (often called STBMs) interact with both immune and endothelial cells. They may contribute to the systemic inflammatory response of both normal and pre-eclamptic pregnancies, although inhibitory activity has also been described. Moreover, trophoblast-derived exosomes may contribute to or cause the downregulation of T cell activity that has been repeatedly observed during pregnancy. Deletion of activate T cells which express Fas ligand by Fas-expressing exosomes derived from trophoblast may contribute to immunoregulation necessary for normal pregnancy.
    Journal of Reproductive Immunology 12/2007; 76(1-2):61-7. DOI:10.1016/j.jri.2007.03.008 · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cellular particles may be larger shed microparticles (>or=100 nm, MPs) that are the products of cell activation or necrosis. There are also smaller endocytic nanoparticles (<100 nm), called exosomes, which are internal vesicles of late endosomes or multivesicular bodies and are released into the extracellular milieu upon fusion of the multivesicular body with the cell surface. Both MPs and exosomes can be detected in the circulations of non-pregnant and pregnant women. In the former MPs are increased in conditions associated with systemic inflammation such as sepsis or metabolic syndrome. During normal pregnancy MPs are increased and they increase further with pre-eclampsia. They include not only MPs derived from platelets, endothelium and various leukocytes but also syncytiotrophoblast derived MPs (often called STBMs). STBMs interact with both immune and endothelial cells and may contribute to the systemic inflammation of both normal and pre-eclamptic pregnancies. However inhibitory activity has also been ascribed to trophoblast derived exosomes. In vitro, they down-regulate T cell activity, a T cell change that has been repeatedly observed, ex vivo, during normal pregnancy.
    Placenta 03/2008; 29 Suppl A:S73-7. DOI:10.1016/j.placenta.2007.11.016 · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Successful pregnancy requires strict temporal regulation of maternal immune function to accommodate the growing fetus. Early implantation is facilitated by inflammatory processes that ensure adequate vascular remodeling and placental invasion. To prevent rejection of the fetus, this inflammation must be curtailed; reproductive immunologists are discovering that this process is orchestrated by the fetal unit and, in particular, the extravillous trophoblast. Soluble and particulate factors produced by the trophoblast regulate maternal immune cells within the decidua, as well as in the periphery. The aim of this review is to discuss the action of recently discovered immunomodulatory factors and mechanisms, and the potential effects of dysregulation of such mechanisms on the maternal immune response that may result in pregnancy loss or preeclampsia.
    Reproduction 03/2011; 141(6):715-24. DOI:10.1530/REP-10-0360