Interferon‐induced class II expression at the spongiotrophoblastic zone of the murine placenta is linked to fetal rejection and developmental abnormalities

Abstract

Type II interferon is known to induce a plethora of gene expression involved in the humoral and cellular immunity. One of the multiple sites of action of gamma-IFN is the fetoplacental unit, where its role has not yet been clearly defined. We have previously shown in vitro that gamma-IFN may induce expression of class II MHC antigens on the spongiotrophoblast layer of the murine placenta, which under physiological conditions is negative for these antigens. Indeed, the absence of class II antigens from the placenta could be part of a mechanism evoked by fetal tissues to escape a host vs. graft reaction. In the present study we show that intraperitoneal in vivo administration of low doses of recombinant gamma-IFN to pregnant females specifically induces class II antigens on the spongiotrophoblast zone, increases fetal abortion, causes retardation of eye development in the fetuses and decreases fetal weight. This treatment also affects the maternal pathology as we witness a prominent hypersplenism in the mother accompanied by low levels of haematocrit, elevated IgG production and decreased granulocytic and thrombocytic counts. These results are specifically linked to the pregnant state of the mother, since virgin females do not develop any of the above abnormalities. Our results not only point to a new dimension in gamma-IFN's role during pregnancy, but may be of clinical importance for prophylaxis since administration of gamma-IFN to a pregnant female may lead to abortion, fetal abnormalities or cause haematologic disorders to the mother.

Maternal Schistosomiasis Japonica Is Associated with Maternal, Placental, and Fetal Inflammation

“…Parasitic diseases, including malaria and leishmaniasis, alter the placental Th2 bias toward a proinflammatory microenvironment and are associated with poor pregnancy outcomes (29,39,48). These data are consistent with animal models of pregnancy that establish that increased systemic and placental gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣) levels produce poor pregnancy outcomes (10,50). They are also consistent with the marked increase in prematurity and IUGR accompanying human pregnancies complicated by systemic proinflammatory diseases, such as systemic lupus erythematosis, rheumatoid arthritis, and falciparum malaria (18,33,55).…”

Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4

“…The dendritic cell (DC), the most potent presenter at the materno-fetal interface, has characteristics of itself, including the predominance of myeloid DCs over lymphoid DCs; high proportion of immature DCs to mature DCs, a moderate expression of CD80/86; co-expression of CD86/HLA-DR; more production of interleukin (IL)-10 than that of IL-12, which is beneficial to the development of 'tolerogenic' DCs and induction of immune tolerance to the embryo (Kammerer et al 2000, Gardner & Moffett 2003, Kammerer et al 2003, Blois et al 2004, Rieger et al 2004. The induced class II antigens expression at the spongiotrophoblastic zone of the murine placenta significantly correlates with fetal abortion and developmental abnormalities (Athanassakis-Vassiliadis et al 1990, Vassiliadis et al 1994). Our present study also found that there was an increased expression of CD80/ 86 and CD28, while a decreased expression of CTLA-4 at the materno-fetal interface in CBA/J!DBA/2 abortionprone models.…”

“…At the materno-fetal interface, the expression of CD80/86 and class II antigens is absent on extravillous trophoblast cells, and mainly localized to antigenpresenting cells (APCs) (Athanassakis- Vassiliadis et al 1990, Vassiliadis et al 1994, Athanassakis et al 1995, Petroff et al 2003. The dendritic cell (DC), the most potent presenter at the materno-fetal interface, has characteristics of itself, including the predominance of myeloid DCs over lymphoid DCs; high proportion of immature DCs to mature DCs, a moderate expression of CD80/86; co-expression of CD86/HLA-DR; more production of interleukin (IL)-10 than that of IL-12, which is beneficial to the development of 'tolerogenic' DCs and induction of immune tolerance to the embryo (Kammerer et al 2000, Gardner & Moffett 2003, Kammerer et al 2003, Blois et al 2004, Rieger et al 2004.…”

Vitamin D and the Regulation of Placental Inflammation

“…Thus, fetal knockout of Cyp27b1 may influence placental IFN-g as a consequence of impaired local synthesis of suppressive 1,25(OH) 2 D 3 . Overabundance of IFN-g, a type 1 Th (Th1) cell cytokine, has been linked to recurrent spontaneous fetal abortion in humans (26,27) and mice (27), implicating Th1 cell adaptive immunity in the pathophysiology of miscarriage. In view of the well-recognized ability of 1,25 (OH) 2 D 3 to promote transition from Th1 cell activity to more tolerant Th2 cell responses (28), it is tempting to speculate that loss of 1,25(OH) 2 D 3 synthesis by the placenta may contribute to a less favorable immune environment during pregnancy.…”