The pathogenesis of preeclampsia (PreE) involves the failure of the maternal immune system to normally tolerate the pregnancy. Inflammatory cytokines are elevated in PreE-affected women with a concurrent decrease in anti-inflammatory cytokine production. Consistent with what other groups have observed in mouse models of hypertension during pregnancy and in human PreE-affected pregnancies, we observed increased inflammatory cytokine production and CD4+ T helper populations in our chronic infusion of vasopressin (AVP) mouse model of PreE. The mechanisms of immune modulation by AVP have not been elucidated. As increased T cell activity is involved in the development of PreE, the objective of this study was to investigate if CD4+ T cells express AVP receptors. Splenic CD4+ T cells were negatively purified from C57BL/6J saline and AVP-infused (24 ng/hour) dams. Expression of AVP receptors (AVPR) 1a, 1b, 2, and the aminopeptidase LNPEP (catalyzes AVP degradation) was determined via qPCR. Raw cycle threshold (Ct) values were normalized (ΔCt) against the 18S rRNA endogenous control. Mouse CD4+ T cells express all AVP receptors and LNPEP. By ANOVA, AVPR2 is the highest expressed receptor in CD4+ T cells from saline (N=7, p=0.002) and AVP-infused (N=10, p<0.0001) dams. Human maternal mononuclear cells, obtained from the University of Iowa Maternal-Fetal Tissue Bank (IRB #200910784) from control and PreE-affected women, were similarly analyzed. As in mouse CD4+ T cells, human control (N=27, p<0.0001) and PreE-affected (N=26, p<0.0001) CD4+ T cells most highly expressed AVPR2. AVPR1a was also highly expressed while AVPR1b was the least expressed. CD4+ T cells isolated from human PreE-affected women expressed significantly lower AVPR1a (10.0±0.3 N=27 vs. 11.1±0.2 N=0.23, p=0.009) and increased LNPEP (17.2±0.5 N=27 vs. 15.1±0.3 N=26, p=0.001) than controls. Here, we demonstrate CD4+ T cells, both mouse and human, express AVP receptors and that 1a and 2 are highest expressed. Although the actions of AVP on the vasculature are primarily mediated through AVPR1a, these data suggest AVP may differentially act through AVPR1a to mediate immune responses during PreE.
Transplantation of bone marrow mononuclear cells decreases seizure incidence, mitigates neuronal loss and modulates pro-inflammatory cytokine production in epileptic rats
