Stranger in a strange land

Abstract

Mammalian mothers and their embryos/fetuses are almost invariably genetically different, which raises the question of how the mother's immune system is diverted so as to permit cohabitation with the 'foreign' body. Several decades of research have shown that multiple cooperative systems sanction uteroplacental immune privilege. These systems include production of several varieties of soluble immunosuppressive molecules in the uterus and the placenta and strict regulation of the molecules expressed on or by placental trophoblast cells. Trophoblast, a unique lineage without counterpart in adult tissues, is in direct contact with maternal blood and tissue. The major graft rejection-promoting molecules, human leukocyte antigens (HLAs), are tightly regulated in these cells, with none of HLA-A, HLA-B, or HLA class II antigens expressed. The HLA class Ib antigens, HLA-E, HLA-F, and HLA-G, are detectable on some subpopulations. Our studies have focused on the expression, regulation, and functions of the soluble isoforms of HLA-G, which circulate in maternal blood and are present at high levels in the pregnant uterus. These isoforms are derived from the single HLA-G gene by alternative splicing and are now known to have immunosuppressive properties. Ours and other studies indicate that soluble HLA-G proteins may comprise a unique tolerogenic system for establishing local immune privilege during pregnancy.

The hidden benefits of sex: Evidence for MHC‐associated mate choice in primate societies

“…Placental expression of foetal MHC class I molecules has been detected in several primate species [75]. These molecules, partially encoded by the paternal haplotype, may represent 'non-self' for the mother but nevertheless contribute to the regulation of the maternal immune response throughout gestation [76]. Consequently, post-insemination MHC-dependent selection may be of particular importance in primates, and account for the higher probability of pregnancy failure reported for couples displaying above-average MHC similarity in humans [77] and macaques [78].…”

HLA-G homodimer-induced cytokine secretion through HLA-G receptors on human decidual macrophages and natural killer cells

“…Although HLA-G has long been known to be uniquely expressed on EVT (9)(10)(11), its role in the placenta is still unclear. HLA-G is unique in two ways: (i) It has only a ''stub'' for a cytoplasmic tail.…”

El embarazo humano: paradigma biológico de tolerancia y adaptación

“…En cambio, expresa HLA-G, especialmente HLA-G5, que tiene por función atenuar la respuesta inmunológica materna 7 .…”