In vivo expression of recombinant pregnancy‐specific glycoprotein 1a induces alternative activation of monocytes and enhances Th2‐type immune response

Abstract

It has been proposed that pregnancy-specific factors could be responsible for shift the balance of cytokine profiles during maternal immune response from Th1-type reactivity into a "less-damaging" Th2-type reactivity. In the present work, we investigated the in vivo function of human pregnancy-specific glycoprotein (PSG)1a, the major variant of PSG polypeptides released into the circulation during pregnancy, on the modulation of the innate and adaptive immune response. For this, BALB/c mice were injected with a vaccinia virus-based vector harboring the human PSG1a cDNA (Vac-PSG1a) 4 days before immunization with ovalbumin (OVA) in complete Freund's adjuvant, and the early specific T cell response against OVA was evaluated 8 days post-immunization. We also studied the activation status of spleen and peritoneal monocytes/macrophages (Mo) populations from Vac-PSG1a-treated mice, and explored whether PSG1a-targeted Mo could affect the Th-type commitment by investigating their impact on the differentiation of naive T cells. Our data show that the treatment with VacPSG1a is able to induce a state of alternative activation on Mo. Furthermore, the generation of the immune response in the context of these alternatively activated antigen-presenting cells may shift T cell differentiation to Th2-type immunity which is more compatible with a successful pregnancy.

Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence of association with maternal vasculature

“…In addition, PSG-mediated suppression of T cells is correlated with increased maternal morbidity in purulent septic complications of abortion (Repina et al 1989), and elevated circulating PSG levels are correlated with improved symptoms of rheumatoid arthritis (Fialova et al 1991). Human and mouse PSGs induce secretion of anti-inflammatory cytokines from monocytes and macrophages in vitro (Wessells et al 2000, Snyder et al 2001, consistent with the observation of PSG-mediated switching of the immune system from a predominantly TH1 response to a predominantly TH2 response, which is considered more compatible with successful pregnancy (Motran et al 2003).…”

“…There is extensive angiogenesis and vascular remodelling associated with pregnancy, and trophoblast giant cells produce a complex array of angiogenic and anti-angiogenic and vasoactive compounds (Cross et al 2002). Currently, Psg are thought to regulate the maternal immune system during pregnancy; however, the evidence in support of this hypothesis has largely been generated in vitro using immune cell models (Wessells et al 2000, Snyder et al 2001, Motran et al 2003, and there remains the possibility that different Psg proteins encode different functions. One interpretation of our finding that Psg may associate with maternal vasculature is that some Psg may exhibit vasoactivity or angiogenesis-related functions.…”

Pregnancy-specific Glycoprotein 1 Induces Endothelial Tubulogenesis through Interaction with Cell Surface Proteoglycans

“…Specifically, PSG1 and some murine PSGs induced endothelial tube formation and the secretion of TGF-␤ 1 and of VEGF-A in different cell types. Interestingly, many different cell types respond to PSG treatment, including monocyte/macrophages, endothelial cells, extravillous trophoblast cells lines, and dendritic cells, and human PSGs have activity in mouse cells (11,13,14). These observations suggest that cells from different origins express the receptor for these proteins, and there is cross-species binding.…”

THE ROLE OF THE DIFFERENT SUBPOPULATIONS OF CD4⁺Т LYMPHOCYTES DURING PREGNANCY

“…Pregnancy specific glycoprotein 1a (PSG1a), produced by syncytiotrophoblast, can macrophagemediately inhibit T lymphocyte proliferation and promote Th2 cytokine secretion [79]. It has been determined that trophoblast expresses receptors for IL-17.…”