Abstract
Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy.
Highlights
The enigma of mammalian pregnancy, which usually succeeds despite genetic differences between the mother and her embryo/fetus, has intrigued immunologists for half a century [1]
Under 2% O2, mRNAs encoding Human Leukocyte Antigens (HLA)-G1 and -G5 were more profoundly enhanced (×7, ×4, respectively) than those encoding HLA-G2 and -G6 (×2, ×2, respectively)
We identified a potential interferon-γ stimulated response element (ISRE) in the 3' untranslated region of Paan-AG that is known to be functional in HLA-A2 but is deleted in HLA-G
Summary
The enigma of mammalian pregnancy, which usually succeeds despite genetic differences between the mother and her embryo/fetus, has intrigued immunologists for half a century [1]. We examine the literature describing the immunological features of the normal maternal-fetal interface describe in detail a novel strategy that has evolved to protect semiallogeneic pregnancy This is high expression in placental cells of membrane-bound and soluble Major Histocompatibility Complex (MHC) antigens with immunosuppressive properties. The second subset of trophoblast cells is characterized by proliferation and migration into the decidua where it performs three well-described major functions These are to (i) anchor the placenta to the uterus, (ii) permit expansion of the uterine spiral arteries to accommodate increased maternal blood perfusion as pregnancy progresses, and (iii) drive the decidual hematopoietic cells into pathways consistent with protection of the fetal semiallograft. Prevents cytolytic killing Inhibits migration Induces apoptosis Induces proliferation, IFNγ production Regulates cytokine production Suppresses cytolytic killing Regulates cytokine production Induces apoptosis Decreases expression of CD8 Decreases proliferation Induces suppressive phenotype Induces TGF-β1 production Reduces stimulatory capacity Alters maturation
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